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Therapy Of Non-Hodgkin's Lymphoma

Follicular lymphomas--a review of treatment modalities.

Unique Identifier: 20323000

Author: Soubeyran P; Debled M; Tchen N; Richaud P; Monnereau A; Bonichon F; Eghbali H

Source: Crit Rev Oncol Hematol 2000 Jul;35(1):13-32

Address: Institut Bergonie, Comprehensive Cancer Centre, 180, rue de Saint-Genes, F-33076 Cedex, Bordeaux, France.

    Follicular lymphoma is the most common low-grade non Hodgkin's lymphoma and represent an homogeneous entity as defined by pathological, molecular and clinical data. This indolent disease is characterised by a slow growth pattern with possible spontaneous regression, is often disseminated but remains incurable with available treatments when disseminated. For localised stages, involved field radiotherapy remains the standard choice but other approaches remain to be investigated. In advanced disease, chemotherapy has been demonstrated to produce high response rates but recent trials with new treatment strategies including interferon and monoclonal antibodies may improve the current situation. In this article, we will review treatment of follicular lymphomas, specially emphasising published phase III trials.

The management of adult aggressive non-Hodgkin's lymphomas.

Unique Identifier: 20323001

Author: Couderc B; Dujols JP; Mokhtari F; Norkowski JL; Slawinski JC; Schlaifer D

Source: Crit Rev Oncol Hematol 2000 Jul;35(1):33-48

Address: Groupe de Radiotherapie et d'Oncologie medicale des Pyrenees (GROP), chemin de l'Ormeau, 65000, Tarbes, France.

    Aggressive non-Hodgkin's lymphona include diffuse large B-cell lymphoma, anaplastic large cell lymphona, and different peripheral T-cell lymphomas. An international prognostic index has been developed including age, serum LDH, performance status, and extranodal involvement. For localized aggressive lymphoma, the preferred treatment is 3-4 CHOP and radiation therapy, with a cure rate of 70-80%. For disseminated aggressive lymphoma, current regimens have a cure rate of less than 40%. Innovative strategies, including dose escalation, autologus stem cell support, new drugs, and immunotherapy are being explored to improve these results.

ASHAP--an effective salvage therapy for recurrent and refractory malignant lymphomas.

Unique Identifier: 20356787

Author: Hanel M; Kroger N; Hoffknecht MM; Peters SO; Metzner B; Fiedler F; Braumann D; Schubert JC; Illiger HJ; Hanel A; Kruger WH; Zeller W; Weh HJ; Hossfeld DK; Zander AR

Source: Ann Hematol 2000 Jun;79(6):304-11

Address: Department of Hematology, Clinic of Internal Medicine III, Chemnitz, Germany.

    BACKGROUND: This study was performed to examine the efficacy and toxicity of the combination of adriamycin (ADR), methylprednisolone (solumedrol), cytarabine (Ara-C), and cisplatin (CDDP) in patients with recurrent and refractory malignant lymphomas. PATIENTS AND METHODS: Sixty-five patients with Hodgkin's disease (HD) (n=14) or non-Hodgkin's lymphomas (NHL) (n = 51) were enrolled in the study. The ASHAP therapy consisted of ADR (40 mg/m2 by continuous infusion (CI) over 96 h), methylprednisolone (500 mg i.v., days 1-5), Ara-C (2 g/m2 as a 2-h infusion on day 5), and CDDP (100 mg/m2 by CI over 96 h). RESULTS: Twenty-five patients (38%) achieved complete remission (CR) and 20 (31%) were taken into partial remission (PR) for an overall response rate of 69%. Thirty-two patients with CR or PR following ASHAP underwent high-dose therapy (HDT) with subsequent hematopoietic stem cell transplantation. After a median follow-up of 52 months, 13 patients are in continuous CR (CCR), the 3-year event-free survival (EFS) was 30% for responders and 21% for all patients. The median overall survival (OS) was 12 months (range 0-70 months), and the OS rate after 3 years was 32%. Unfavorable prognostic factors for EFS and OS by univariate analysis were an elevated value of the serum lactate dehydrogenase and refractory lymphoma. The most frequently observed side effects following ASHAP were leukocytopenia and thrombocytopenia of World Health Organization (WHO) grades III/IV in approximately 80% of all courses. Non-hematological toxicities such as gastrointestinal side effects, infections, mucositis, renal and neurotoxicity occurred more rarely and reached WHO grades III/IV only occasionally. No treatment-related mortality with ASHAP was observed. CONCLUSIONS: ASHAP is an effective and moderately toxic salvage therapy for patients with recurrent or refractory HD and NHL. The results in patients responding to ASHAP and afterwards undergoing HDT with stem cell support are comparable with other established protocols and indicate an improvement in survival if HDT is carried out as intensification.

FLUDAP: salvage chemotherapy for relapsed/refractory aggressive non-Hodgkin's lymphoma.

Unique Identifier: 20214656

Author: Child JA; Johnson SA; Rule S; Smith GM; Morgan GJ; Johnson PW; Prentice AG; Tollerfield SM; Wareham E

Source: Leuk Lymphoma 2000 Apr;37(3-4):309-17

Address: Department of Haematology, The General Infirmary, Leeds, UK.

    The aim of this study was to investigate the combination of fludarabine phosphate, dexamethasone, cytosine arabinoside and cis-platinum (FLUDAP) in the treatment of patients with relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL). This regimen comprises: dexamethasone 100 mg/d continuous infusion (cont. inf.) d1-3; cytosine arabinoside (ara-C) 1 g/m2/d cont. inf. d 2,3; fludarabine phosphate 30 mg/m2 short inf. 4hr prior to each 24hr ara-C inf.; cis-platinum 50 mg/m2 4hr inf. at the start of each 24hr ara-C inf. G-CSF (lenograstim, Granocyte) is given at 263 microg s.c. daily from day 7 until the neutrophil count reaches 1.0x10(9)/l. The regimen repeats at 21 day intervals. A total of 33 patients were registered (median age 47 years; 24 males, 9 females); the majority (73%) were refractory to their previous treatment and most had advanced disease by Ann Arbor stage. Thirteen (39%) of the 33 enrolled patients (52% of the 25 fully evaluable patients who received at least 2 courses of FLUDAP) responded to treatment. A maximum response of complete remission was achieved in 5 patients, good partial remission in 3, and partial remission in 5. Twelve patients went on to successful stem cell supported intensification therapy. Median survival times were higher in the responding patients, and in those patients transplanted post-FLUDAP. The toxicity associated with the FLUDAP regimen was generally predictable; frequently reported severe events included haematological toxicity and infection. In conclusion, the FLUDAP regimen shows promise as a salvage regimen and increases the available therapeutic options in the treatment of recurrent/refractory aggressive NHL.

A predictive model for life-threatening neutropenia and febrile neutropenia after the first course of CHOP chemotherapy in patients with aggressive non-Hodgkin's lymphoma.

Unique Identifier: 20214660

Author: Intragumtornchai T; Sutheesophon J; Sutcharitchan P; Swasdikul D

Source: Leuk Lymphoma 2000 Apr;37(3-4):351-60

Address: Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

    The purpose of this study was to develop a model for predicting the occurrence of life-threatening neutropenia (LN, ANC < or = 0.5 x 10(9)/l) and febrile neutropenia (FN, an ANC < 0.5x10(9)/l in association with a body temperature of > or = 38.3 degrees C) after the first cycle of CHOP therapy in patients newly diagnosed with aggressive NHL. One hundred and forty-five patients, aged > or = 15 years, with newly diagnosed diffuse mixed, diffuse large-cell or large-cell immunoblastic lymphoma (IWF categories, F, G, H), who had been treated with CHOP at King Chulalongkorn Memorial Hospital between June 1994 and December 1998, were entered into the study. The criteria for eligibility included complete work-up for baseline evaluation, treatment with standard CHOP chemotherapy, at least one complete blood count performed during days 8-14 post-treatment or if at any time the patients experienced a BT of > or = 38.3 degrees C and were not treated with any colony-stimulating factors (CSFs). The median age of the patients was 47 years (range, 17-78). Forty-eight percent of the patients were in stage III/IV, 36% had ECOG performance status (PS) II-IV, 30% had > or = 2 extranodal diseases, 59% had serum LDH > 1 x normal and 23% had bone marrow involvement. The frequencies of patients in the low-, low-intermediate, high-intermediate and high risk groups according to the international index were 29%, 28%, 17% and 26%, respectively. Thirty-nine percent of the patients had LN at nadir and 33% developed FN after the first course of CHOP. By using stepwise logistic regression analysis, the pretreatment variables independently predictive of the LN at nadir and the FN were serum albumin concentration of < or = 3.5 g/dl, serum LDH > 1 x normal and whether there was bone marrow involvement of lymphoma at presentation. The model, based on the incorporation of these three factors, identified three risk groups of patients with a predicted probability of developing LN at nadir of 81.5% (95% CI, 68.5-90.7) (high risk), 23.9% (95% CI, 12.6-38.8) (intermediate risk) and 4.4% (95% CI, 0.5-15.1) (low risk). The predicted rate of FN in the three groups were 72.2% (95% CI, 58.4-83.5), 17.4% (95% CI, 7.8-31.4) and 2.2% (95% CI, 0.05-11.8), respectively. In conclusion, our model could be used as a means to identify patients with newly diagnosed aggressive NHL, treated with CHOP, who are at high risk (> or = 50% probability) of developing post-first course LN and FN, in whom CSF and/or antibiotic prophylaxis might be indicated.

T-cell infiltrate after monoclonal anti-CD20 antibody therapy for B-cell lymphoma.

Unique Identifier: 20214664

Author: Vincent-Salomon A; Mathiot C; Macintyre E; Girre V; Fourquet A; Mercier C; Freneaux P; Dumont J; Decaudin D

Source: Leuk Lymphoma 2000 Apr;37(3-4):387-91

Address: Department of Tumor Biology, Institut Curie, Paris, France.

    No abstract available.

A phase I study of combination therapy with immunotoxins IgG-HD37-deglycosylated ricin A chain (dgA) and IgG-RFB4-dgA (Combotox) in patients with refractory CD19(+), CD22(+) B cell lymphoma.

Unique Identifier: 20239226

Author: Messmann RA; Vitetta ES; Headlee D; Senderowicz AM; Figg WD; Schindler J; Michiel DF; Creekmore S; Steinberg SM; Kohler D; Jaffe ES; Stetler-Stevenson M; Chen H; Ghetie V; Sausville EA

Source: Clin Cancer Res 2000 Apr;6(4):1302-13

Address: Developmental Therapeutics Program, Clinical Trials Unit, Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892-1906, USA.

    This study used an 8-day continuous infusion regimen of a 1:1 mixture of two immunotoxins (ITs) prepared from deglycosylated ricin A chain (dgA) conjugated to monoclonal antibodies directed against CD22 (RFB4-dgA) and CD19 (HD37-dgA; Combotox) in a Phase I trial involving 22 patients with refractory B cell lymphoma to determine the maximum tolerated dose, clinical pharmacology, and toxicity profile and to characterize any clinical responses. Adult patients received a continuous infusion of Combotox at 10, 20, or 30 mg/m2/192 h. No intrapatient dose escalation was permitted. Patients with > or =50 circulating tumor cells (CTCs)/mm3 in peripheral blood tolerated all doses without major toxicity. The maximum level of serum IT (Cmax) achieved in this group was 345 ng/ml of RFB4-dgA and 660 ng/ml of HD37-dgA (1005 ng/ml of Combotox). In contrast, patients without CTCs (<50/mm3) had unpredictable clinical courses that included two deaths probably related to the IT. Additionally, patients exhibited a significant potential for association between mortality and a history of either autologous bone marrow or peripheral blood stem cell transplants (P2 = 0.003) and between mortality and a history of radiation therapy (P2 = 0.036). In patients with CTCs, prior therapies appeared to have little impact on toxicity. Subsequent evaluation of the ITs revealed biochemical heterogeneity between two lots of HD37-dgA. In addition, HD37-dgA thawed at the study site tended to contain significant particulates, which were not apparent in matched controls stored at the originating site. This suggests that a tendency to aggregate may have resulted from shipping, storage, and handling of the IT that occurred prior to preparation for administration. It is not clear to what extent, if any, the aggregation of HD37-dgA IT was related to the encountered clinical toxicities; however, the potential to aggregate does suggest one possible basis for problems in our clinical experience with HD37-dgA and leads us to the conclusion that non-aggregate-forming formulations for these ITs should be pursued prior to future clinical trials.

[Duodenal Burkitt lymphoma in an HIV-negative patient: a medical emergency (letter)]

Unique Identifier: 20304716

Author: Foa C; Magne N; Francois E; Peroux JL; Pivot X; Thyss A

Source: Gastroenterol Clin Biol 2000 Apr;24(4):470-1

    No abstract available.

Experience with total skin electron beam therapy in combination with extracorporeal photopheresis in the management of patients with erythrodermic (T4) mycosis fungoides.

Unique Identifier: 20323326

Author: Wilson LD; Jones GW; Kim D; Rosenthal D; Christensen IR; Edelson RL; Heald PW; Kacinski BM

Source: J Am Acad Dermatol 2000 Jul;43(1 Pt 1):54-60

Address: Departments of Therapeutic Radiology and Dermatology, Yale University School of Medicine, New Haven, CT 06520-8040, USA.

    OBJECTIVE: We compared the prognosis of patients with erythrodermic mycosis fungoides (MF) administered total skin electron beam radiation (TSEB) plus neoadjuvant, concurrent, and adjuvant extracorporeal photopheresis (ECP) with the prognosis of patients administered only TSEB. Outcomes of clinical interest include disease-free survival (DFS), progression-free survival (PFS), overall survival (OS), and cause-specific survival (CSS). METHODS: This study was a retrospective nonrandomized series. Between 1974 and 1997, a total of 44 patients with erythrodermic MF from the Department of Therapeutic Radiology, Yale University School of Medicine, and the Department of Radiation Oncology, Cancer Care Ontario, Hamilton, Ontario, were collected and analyzed as a group (Hamilton = 15, Yale = 29). These patients received TSEB consisting of 32 to 40 Gy via 4 to 6 MeV. Twenty-one patients at Yale also received ECP treatment 2 days per month for a median of 6 months. Median age was 68 years (range, 29-82 years) at the commencement of TSEB, and 66% were male. Seventy-three percent of patients had received other therapies before TSEB, including 75 courses that failed to control disease (n = 15 systemic therapy, 16 biologicals, and 44 topical therapies). At TSEB, 59% had hematologic involvement (B1), 30% were stage IVA (N3), and 13% were IVB (M1). Median follow-up was 2.2 years (range, 0.3-13.9 years) subsequent to TSEB and 3.7 years from diagnosis (range, 0.8-16.8 years). RESULTS: All patients responded to TSEB within 2 months of completion, with a cutaneous complete response rate of 73%. For the 32 complete responders the 3-year DFS was 63%. It was 49% for those 17 patients who received only TSEB compared with 81% for those 15 patients who received TSEB + ECP. Cox regression analysis demonstrated that ECP was associated with prolonged remission (DFS multivariate P =.024, adjusting for B1 and stage). The 2-year PFS, CSS, and OS for the TSEB group were 36%, 69%, and 63%, respectively, compared with 66%, 100%, and 88% for the TSEB + ECP cohort. Cox regression demonstrated that ECP was associated with CSS (multivariate P =.048, adjusting for B1 and stage). For those who progressed, a total of 49 subsequent courses of therapy were administered (n = 20 chemotherapy, 10 biologicals, and 19 topical therapies). Thirteen patients died from MF-related causes, and 8 died from other causes. Acute and chronic toxicities were consistent with those previously reported. CONCLUSION: ECP given concurrently with, or immediately after, TSEB (32-40 Gy) significantly improves both PFS and CSS for patients with erythrodermic MF compared with TSEB without the addition of ECP.

Primary and secondary cutaneous CD30(+) lymphoproliferative disorders: a report from the Dutch Cutaneous Lymphoma Group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment.

Unique Identifier: 20304461

Author: Bekkenk MW; Geelen FA; van Voorst Vader PC; Heule F; Geerts ML; van Vloten WA; Meijer CJ; Willemze R

Source: Blood 2000 Jun 15;95(12):3653-61

Address: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.

    To evaluate our diagnostic and therapeutic guidelines, clinical and long-term follow-up data of 219 patients with primary or secondary cutaneous CD30(+) lymphoproliferative disorders were evaluated. The study group included 118 patients with lymphomatoid papulosis (LyP; group 1), 79 patients with primary cutaneous CD30(+) large T-cell lymphoma (LTCL; group 2), 11 patients with CD30(+) LTCL and skin and regional lymph node involvement (group 3), and 11 patients with secondary cutaneous CD30(+) LTCL (group 4). Patients with LyP often did not receive any specific treatment, whereas most patients with primary cutaneous CD30(+) LTCL were treated with radiotherapy or excision. All patients with skin-limited disease from groups 1 and 2 who were treated with multiagent chemotherapy had 1 or more skin relapses. The calculated risk for systemic disease within 10 years of diagnosis was 4% for group 1, 16% for group 2, and 20% for group 3 (after initial therapy). Disease-related 5-year-survival rates were 100% (group 1), 96% (group 2), 91% (group 3), and 24% (group 4), respectively. The results confirm the favorable prognoses of these primary cutaneous CD30(+) lymphoproliferative disorders and underscore that LyP and primary cutaneous CD30(+) lymphomas are closely related conditions. They also indicate that CD30(+) LTCL on the skin and in 1 draining lymph node station has a good prognosis similar to that for primary cutaneous CD30(+) LTCL without concurrent lymph node involvement. Multiagent chemotherapy is only indicated for patients with full-blown or developing extracutaneous disease; it is never or rarely indicated for patients with skin-limited CD30(+) lymphomas. (Blood. 2000;95:3653-3661)

Quality of life-adjusted survival analysis of high-dose therapy with autologous bone marrow transplantation versus sequential chemotherapy for patients with aggressive lymphoma in first complete remission. Groupe d'Etude les Lymphomes de l'Adulte (GELA).

Unique Identifier: 20304466

Author: Mounier N; Haioun C; Cole BF; Gisselbrecht C; Sebban C; Morel P; Marit G; Bouabdallah R; Ravoet C; Salles G; Reyes F; Lepage E

Source: Blood 2000 Jun 15;95(12):3687-92

Address: Departement d'information hospitalier and Service d'hematologie clinique Hopital Henri Mondor, AP-HP, Creteil, France.

    Evaluating high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) in term of both duration and quality of life (QOL) presents major interests for patients with non-Hodgkin lymphoma. The quality-adjusted time without symptom and toxicity (Q-TWiST) methodology was applied to the LNH87-2 trial comparing HDT with ASCT versus sequential chemotherapy in 541 patients in first complete remission (CR). Overall survival (OS) and disease-free survival (DFS) curves were used to estimate duration of 4 health states: acute short-term toxicity (Tox1), secondary toxicity (Tox2), time without symptom and toxicity (TWiST), and relapse (Rel). Areas under survival curves (AUC) were retrospectively weighted according to QOL coefficients. HDT increased, but not significantly, TWiST (+2. 4 months in AUC, P =.17) and decreased Rel (-3 months, P <.01). Survival estimates did not differ between the 2 treatments (AUC 47.7 months for OS, 39.7 months for DFS). High-risk patients treated by HDT versus chemotherapy had a significant benefit in DFS (AUC 28.8 versus 24.9 months, P <.01) but not in OS (AUC 37.3 versus 36 months, P =.27). Sensitivity analysis, performed by varying QOL coefficients, demonstrated significant quality-adjusted survival gain in high-risk patients treated by HDT. In low-risk patients, a diagram provided an aid to clinical decision-making. This analysis supports the use of HDT in these patients with adverse prognostic factors in the first CR, even after adjusting for QOL using the Q-TWiST method. (Blood. 2000;95:3687-3692)

High incidence of symptomatic cytomegalovirus infection in multiple myeloma patients undergoing autologous peripheral blood stm cell transplantation [letter]

Unique Identifier: 20395163

Author: Alessandrino EP; Varettoni M; Colombo AA; Caldera D; Bernasconi P; Malcovati L

Source: Blood 2000 Jun 15;95(12):4016-8

    No abstract available.

Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies.

Unique Identifier: 20351982

Author: Flinn IW; Byrd JC; Morrison C; Jamison J; Diehl LF; Murphy T; Piantadosi S; Seifter E; Ambinder RF; Vogelsang G; Grever MR

Source: Blood 2000 Jul 1;96(1):71-5

Address: Johns Hopkins Oncology Center, Baltimore, MD, USA.

    To evaluate the response rate and potential toxicities, a phase II trial was conducted of fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated low-grade and select intermediate-grade lymphoid malignancies. Symptomatic patients with preserved end organ function received cyclophosphamide 600 mg/m(2) intravenous (iv) day 1 and fludarabine 20 mg/m(2) iv days1 through 5, followed by filgrastim 5 microg/kg subcutaneous starting approximately day 8. Treatment was repeated every 28 days until maximum response or a maximum of 6 cycles. Sixty patients, median age 53.5 years, were enrolled. Thirty-seven patients with non-Hodgkin lymphoma (NHL) were stage IV and 6 were stage III. Eleven of 17 patients with chronic lymphocytic leukemia (CLL) were Rai intermediate risk and 6 were high risk. The overall complete response (CR) rate was 51% and the partial response (PR) rate was 41%. Of patients with CLL, 47% achieved a CR and the remaining 53% achieved a PR. Of patients with follicular lymphoma, 60% achieved CR and 32% achieved a PR. Although the toxicity of this regimen was mainly hematologic, significant nonhematologic toxicities, including infections, were seen. Twenty-four patients subsequently received an autologous or allogeneic stem cell transplant. Engraftment was rapid, and there were no noticeable procedure toxicities in the immediate posttransplant period attributable to the fludarabine and cyclophosphamide regimen. Fludarabine, cyclophosphamide, and filgrastim make up a highly active and well-tolerated regimen in CLL and NHL.

A randomized, double-blind trial of filgrastim (granulocyte colony-stimulating factor) versus placebo following allogeneic blood stem cell transplantation.

Unique Identifier: 20351984

Author: Bishop MR; Tarantolo SR; Geller RB; Lynch JC; Bierman PJ; Pavletic ZS; Vose JM; Kruse S; Dix SP; Morris ME; Armitage JO; Kessinger A

Source: Blood 2000 Jul 1;96(1):80-5

Address: Department of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.

    Blood stem cell transplantation (BSCT) results in rapid hematopoietic recovery in both the allogeneic and autologous transplant settings. Because of the large numbers of progenitor cells in mobilized blood, the administration of growth factors after transplantation may not provide further acceleration of hematopoietic recovery. A randomized, double-blind, placebo-controlled study was performed to determine the effects of filgrastim (granulocyte colony-stimulating factor; G-CSF) administration on hematopoietic recovery after allogeneic BSCT. Fifty-four patients with hematologic malignancies undergoing a related, HLA-matched allogeneic BSCT were randomly assigned to receive daily filgrastim at 10 microg/kg or placebo starting on the day of transplantation. A minimum of 3 x 10(6) CD34(+) cells/kg in the allograft was required for transplantation. All patients received a standard preparative regimen and a standard regimen for the prevention of graft-versus-host disease (GVHD). The median time to achieve an absolute neutrophil count greater than 0.5 x 10(9)/L was 11 days (range, 9-20 days) for patients who received filgrastim compared with 15 days (range, 10-22 days) for patients who received placebo (P =.0082). The median time to achieve a platelet count greater than 20 x 10(9)/L was 13 days (range, 8-35 days) for patients who received filgrastim compared with 15.5 days (range, 8-42 days) for patients who received placebo (P =.79). There were no significant differences for red blood cell transfusion independence, the incidence of acute GVHD, or 100-day mortality between the groups. The administration of filgrastim appears to be a safe and effective supportive-care measure following allogeneic BSCT.

Primary treatment of low-grade non-Hodgkin's lymphoma using an all oral anthracycline-containing regimen, chlorambucil, idarubicin, dexamethasone (CID)--a phase II study.

Unique Identifier: 20367708

Author: Taylor PR; Jackson GH; Galloway MJ; Soukop M; Tinegate H; Angus B; Proctor SJ

Source: Cancer Chemother Pharmacol 2000;46(1):63-8

Address: Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.

    PURPOSE: The majority of patients with low-grade non-Hodgkin's lymphoma (LGNHL) are in the older age groups and are thus less able to tolerate aggressive treatment. Chlorambucil, alone and in combination, has been widely accepted as the initial treatment of choice for many years. The availability of an anthracycline which could be given orally in combination with chlorambucil and steroid led us to investigate the efficacy and toxicity of this novel regimen. METHODS: Patients (age less than 70 years) with a histologically confirmed diagnosis of LGNHL (Kiel classification) were eligible for the study if they had no previous chemotherapy. Treatment consisted of chlorambucil 20 mg/ m2 daily for 3 days given on each day in three divided doses, idarubicin 10 mg/m2 for 3 days before breakfast, and dexamethasone 4 mg twice daily for 5 days. All drugs were given orally. Treatment was repeated every 21 days for a maximum of six courses. The regimen was assessed for toxicity and response. RESULTS: A total of 72 patients were registered, and 64 were eligible (median age 52 years). Toxicity was assessed for all cycles given (347). The predominant toxicity was haematological, but in only one course did grade 4 neutropenia (less than 0.5 x 10(9)) occur. Alopecia was not a problem. Full doses of the treatment were administered to 40% of the patients, with no delays or dose reductions. The overall response rate was 83%. Six patients had static disease and two progressed on treatment. Lactate dehydrogenase (LDH) was found to be a good predictor of response to treatment. Of 12 patients documented to have raised LDH, 5 failed to respond to treatment, compared to 1 of 32 patients who had a normal LDH (chi2 10.65, P < 0.002). With a minimum follow-up of 4 years for all patients actuarial 5-year event-free survival was 22% and overall survival was 65%. However, in patients with best and intermediate risk LGNHL (by the SNLG Prognostic Index for Low Grade Disease) overall survival are 88% and 64%, respectively. CONCLUSIONS: This novel regimen was effective and well tolerated.

Long-term follow-up of autologous stem-cell transplantation for follicular and transformed follicular lymphoma.

Unique Identifier: 20370619

Author: Berglund A; Enblad G; Carlson K; Glimelius B; Hagberg H

Source: Eur J Haematol 2000 Jul;65(1):17-22

Address: Department of Oncology, Uppsala University, Akademiska sjukhuset, Sweden.

    Despite the fact that follicular lymphomas are both chemo- and radiosensitive, the disease is generally non-curable. These lymphomas often undergo transformation to a more malignant state. In order to improve the prognosis, high-dose treatment with stem cell support has been tested, but its role in the treatment of this disease is still unclear. Fourteen men and eight women with a median age of 45 yr (34-59) were treated with high-dose therapy with autologous stem cell transplantation between 1987 and 1996. The patients were selected to undergo intensive therapy because of an estimated short survival (median < 3 yr), even though they had chemosensitive disease and adequate performance status. Eleven patients' lymphomas had transformed, and the other eleven patients had one or more unfavourable prognostic signs such as advanced stage, bulky disease, multiple relapses, or short remission duration. The conditioning regimen has varied over the period, but BEAC (Becenum, etoposide, cytarabine, cyclophosphamide) or etoposide/cyclophosphamide with or without total body irradiation (TBI) was used in most patients. Nine patients had their stem cells purged. After a median follow-up time of 74 months overall survival was 81% and disease-free survival 72%. One toxic procedure-related death occured. There was no difference in outcome between patients with a transformed lymphoma compared to those without transformation. The patients treated with TBI had a significantly worse outcome. Toxicity was also much higher in TBI-treated patients, including four cases of secondary malignancy (three myelodysplastic syndrome (MDS) cases and one patient with breast carcinoma). This retrospective study, with the longest follow-up time so far reported, shows a promising 6-yr DFS of 72% in a group of follicular lymphoma patients with a bad prognosis. The outcome of patients with transformed lymphoma compared to historical controls is especially encouraging. The high incidence of MDS is worrying. The role of TBI should be questioned because this and other studies have not shown any advantage of using TBI. In the absence of randomised trials the role of high-dose treatment for patients with follicular lymphoma is still not defined.

The outcome of combined-modality treatments for stage I and II primary large B-cell lymphoma of the mediastinum.

Unique Identifier: 20349476

Author: Nguyen LN; Ha CS; Hess M; Romaguera JE; Manning JT; Cabanillas F; Cox JD

Source: Int J Radiat Oncol Biol Phys 2000 Jul 15;47(5):1281-5

Address: Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

    PURPOSE: Primary mediastinal large B-cell lymphoma (PML) has clinicopathologic features distinct from those of other diffuse large-cell lymphomas. However, the optimal treatment for this tumor is evolving, and in particular, the role of radiation therapy remains undefined. We conducted a retrospective review to evaluate the role of radiation therapy in this disease. METHODS AND MATERIALS: The medical records of 40 consecutive patients with Ann Arbor Stage I or II PML treated at our institution from January 1980 to December 1995 were reviewed. There were 18 patients with Stage I disease and 22 patients with Stage II disease; 62.5% were women and 37.5% were men. The median age was 32.4 years (range, 17-74 years). The tumor scores were 0 in 1 patient, I in 5 patients, II in 13 patients, III in 7 patients, IV in 4 patients, and unknown in 10 patients. The International Prognostic Index (IPI) was 0 in 10 patients, I in 26 patients, II in 2 patients, and unknown in 2 patients. All patients were treated with doxorubicin-based chemotherapy, and 35 patients received radiation therapy. For most patients who received radiation therapy, an involved field or a modified-mantle field was used, and a dose of 40 Gy in 20 fractions or 39.6 Gy in 22 fractions was administered. Univariate analysis was performed to identify prognostic factors. RESULTS: The median follow-up in surviving patients was 56 months (range, 19-194 months). The actuarial 5-year relapse-free survival (RFS) rate and overall survival (OS) rate for all patients were 67% and 72%, respectively. Thirty-five patients achieved a complete response; 32 of these patients received radiation therapy. The patterns of failure for the complete responders were as follows: locoregional failure alone for 1 patient (at the margin of the radiation field); distant failure alone for 5 patients; and both locoregional (in-field) and distant failure for 1 patient. There were no failures after 2.5 years. None of the 5 patients who never achieved a complete response had local control, and all died with disease. Only 2 of the 5 completed the planned course of radiation therapy; both had massive mediastinal disease. There was no treatment-related death from the initial chemotherapy or radiation therapy. One patient developed a second malignancy (sarcoma) within the radiation field after 13 years. The tumor score was a significant predictor of RFS (p = 0.016) and OS (p = 0.006), but the IPI did not prove to be a significant predictor. CONCLUSION: We recommend consolidative radiation therapy in view of the excellent local control and the lack of significant toxicity. Modified mantle or involved field appears to be an adequate volume, and 39.6-40 Gy appears to be an adequate dose. The tumor score is a significant prognostic factor.

Treatment-related acute gastric bleeding managed successfully with surgical devascularization.

Unique Identifier: 20370508

Author: Kelessis NG; Vassilopoulos PP; Lambrinakis PM; Zissis CG; Efremidou AI

Source: J Surg Oncol 2000 Jun;74(2):138-40

Address: 1st Surgical Oncology Clinic, Saint-Savvas Anticancer Hospital, Athens, Greece.

    BACKGROUND AND OBJECTIVES: Patients with gastric lymphoma treated by chemotherapy or radiation therapy are at high risk of developing complications, most commonly perforation or bleeding. In any case of upper gastrointestinal tract bleeding during conservative treatment for gastric lymphoma, thorough investigation is required to exclude other causes of hemorrhage which could be managed appropriately. When the source of bleeding is the tumor, the only effective measure is resection of the stomach, a very dangerous operation in these poor-risk patients. METHODS: We treated 3 consecutive patients with life-threatening gastric bleeding from lymphoma treated by chemotherapy. RESULTS: We successfully controlled the hemorrhage by surgical devascularization. CONCLUSION: Devascularization of the involved part of the stomach is safe and effective.

[Diagnosis and treatment of non-Hodgkin lymphoma in Netherlands: variation in guidelines and in practice]

Unique Identifier: 20355493

Author: Faber LM; van Agthoven M; Uyl-de Groot CA; Lowenberg B; Huijgens PC

Source: Ned Tijdschr Geneeskd 2000 Jun 17;144(25):1223-7

Address: Academisch Ziekenhuis Vrije Universiteit, afd. Hematologie, Amsterdam.

    OBJECTIVE: To investigate current guidelines for diagnosis and treatment of intermediate or high grade non-Hodgkin's lymphoma (NHL), stage I-IV (Burkitt's and lymphoblastic lymphoma excluded) and to compare this with current clinical practice. DESIGN: Descriptive. METHOD: An inventory of guidelines for diagnosis and treatment of NHL of the Regional Cancer Centres (RCCs) was made in mid-1998, an enquiry containing questions about the practical situation concerning the diagnosis and treatment of NHL patients was sent to 59 internists-haematologists in non-university hospitals of the RCC regions Amsterdam, Rotterdam and South. RESULTS: Apart from the standard diagnostics, the RCCs recommended several examinations for staging. For the initial staging the haematologists not always requested the recommended CTs of chest and abdomen and most of them did no restaging after the last course of chemotherapy. Half of them left the assessment of lymph node biopsy samples to a lymphoma panel. The recommended primary treatment consisted mainly of chemotherapy with cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP). In certain regions, the schedule was slightly changed, with additional tenoposide and bleomycin (CHVmP/BV). The treatment schedules were heterogeneous, especially for stage I NHL. In leukopenia and/or thrombocytopenia, postponement was recommended, but dosage reduction was carried out immediately, especially in older patients, sometimes with administration of a haemopoietic growth factor. Recurrence NHL was treated in accordance with the guidelines with second-line chemotherapy, if possible followed by peripheral stem cell transplantation in a haematooncological centre. CONCLUSION: Considering these results development of national guidelines for NHL would seem to be desirable.

Novel surveillance and cure of a donor-transmitted lymphoma in a renal allograft recipient.

Unique Identifier: 20374245

Author: Herzig KA; Falk MC; Jonsson JR; Axelsen RA; Griffin AD; Hawley CM; Rigby RJ; Cobcroft R; Nicol DL; Powell EE; Johnson DW

Source: Transplantation 2000 Jul 15;70(1):149-52

Address: University of Queensland Department of Surgery, Princess Alexandra Hospital, Woolloongabba, Australia.

    BACKGROUND: In this report we describe a malignant lymphoma of donor origin inadvertently transplanted into two renal allograft recipients, despite standard comprehensive donor screening. The successful clearance of the tumor from both patients and a novel method of surveillance are detailed. METHODS: Initial management consisted of withdrawal of immunosuppression to promote rejection of the allograft and the transplanted tumor in both patients, followed by graft removal. Peripheral blood microchimerism was assessed in both recipients using nested polymerase chain reaction to detect the DYZ3 gene on the Y chromosome (donor male, recipients female). RESULTS: Although microchimerism was detected on day 6 after transplantation and day 1 after explantation, repeat peripheral blood examination at 1, 3, and 6 months after explantation demonstrated no microchimerism. Both patients remain well at 12 months and have been relisted for transplantation. CONCLUSION: Despite inadvertent transplantation of a previously undiagnosed malignancy of donor origin, the recipients' immune response was able to eliminate donor tumor cells after the withdrawal of immunosuppression. Repeated surveillance of peripheral blood from both recipients, using a novel application of the technique of nested polymerase chain reaction to amplify donor DNA, demonstrated no persistence of donor cells, supporting effective eradication of the donor malignancy.

[A case of malignant lymphoma of the epididymis]

Unique Identifier: 20303585

Author: Suzuki K; Sai S; Kato K; Murase T

Source: Hinyokika Kiyo 2000 Apr;46(4):291-3

Address: Department of Urology, Red Cross Nagoya First Hospital.

    A 17-year-old man visited our hospital with the chief complaint of painless swelling of the left scrotal content. An elastic hard mass was palpable at the upper pole of the left testis. Left radical orchiectomy was performed. The tumor originated from the epididymis and did not involve the testis or the spermatic cord. Histologically, the tumor was diagnosed as a malignant lymphoma (non-Hodgkin's lymphoma, diffuse mixed cell type, B-cell type). No abnormalities were found in other organs. After establishment of the diagnosis of primary epididymal malignant lymphoma, 3 courses of chemotherapy (adriamycin, vincristine, cyclophosphamide, prednisolone) were performed. No evidence of recurrence or metastasis was found 26 months after surgery.

The gastric marginal zone B-cell lymphoma of MALT type.

Unique Identifier: 20346886

Author: Zucca E; Bertoni F; Roggero E; Cavalli F

Source: Blood 2000 Jul 15;96(2):410-9

Address: Oncology Institute of Southern Switzerland, Department of Medical Oncology, Bellinzona, Switzerland.

    No abstract available.

The prednisone dosage in the CHOP chemotherapy regimen for non-Hodgkin's lymphomas (NHL): is there a standard?

Unique Identifier: 20345617

Author: Moreno A; Colon-Otero G; Solberg LA Jr

Source: Oncologist 2000;5(3):238-49

Address: Mayo Graduate School of Medicine and Division of Hematology/Oncology, The Mayo Clinic, Jacksonville, Florida 32224, USA.

    PURPOSE: Discrepancies in the quoted prednisone dosages in the regimens reported as the only standard CHOP regimen stimulated our interest in reviewing the medical literature regarding this issue and to assess whether practicing hematologists and oncologists in the U.S. are aware of the different dose schedules of prednisone in the published CHOP programs. METHODS: Sixteen textbooks and chemotherapy reference books were reviewed. A MEDLINE search of English-language articles published between January 1970 and December 1998 was performed. An eight-point questionnaire was sent via e-mail with responses obtained from 421 hematology/oncology physicians in the U.S. RESULTS: Sixteen textbooks and chemotherapy reference books reviewed quoted only one prednisone dosage as part of the standard CHOP regimen; the prednisone dosages quoted as standard varied between publications. More than 4,000 eligible non-Hodgkin's lymphoma patients have been treated with the CHOP chemotherapy as part of 43 different clinical trials reviewed. The dosages of prednisone and prednisolone used varied among six different levels. Thirty percent (127/421) of practicing U.S. physicians were not aware of the existence of more than one prednisone dose schedule as part of the CHOP regimen. The three most frequently used dosages are 100 mg/days 1-5 (67%), 100 mg/m(2)/days 1-5 (17%), and 60 mg/m(2)/days 1-5 (13%). CONCLUSIONS: Discrepancies in steroid dosages used as part of the reported standard CHOP regimens are common and not well recognized in the medical literature nor by practicing U.S. hematologists/oncologists. Based on this study, a prednisone dose of 100 mg/day for five days should be considered the standard dose.

A variant of ProMACE-CytaBOM chemotherapy for non-Hodgkin's lymphoma with threefold higher drug dose size but identical cumulative dose intensity. A pilot study of the Italian lymphoma study group (GISL).

Unique Identifier: 20169252

Author: Gobbi PG; Ghirardelli ML; Avanzini P; Baldini L; Quarta G; Stelitano C; Broglia C; Loni C; Silingardi V; Ascari E

Source: Haematologica 2000 Mar;85(3):263-8

Address: Medicina Interna e Oncologia Medica, Universita di Pavia, Policlinico S. Matteo, P.le Golgi 2, 27100 Pavia, Italy.

    BACKGROUND AND OBJECTIVE: The positive results of high-dose chemotherapy followed by rescue with bone marrow progenitor cell transplantation are generally ascribed to the high dose size (DS) of the drugs given. However, a concomitant marked increase in dose intensity (DI) is always involved. With the aim of comparing the role of DS and DI in non-Hodgkin's lymphomas, a variant of Fisher's ProMACE-CytaBOM regimen was designed in which the projected cumulative drug DIs remained the same as in the original schedule but the DSs were tripled. DESIGN AND METHODS: Dosages in mg/m(2), route and days of administration were the following: cyclophosphamide 1,950 i.v. on days 1, 64; methotrexate 360 i.v. days 15, 78; vincristine 1.4 iv days 15, 78, 43, 106; etoposide 360 i.v. days 29, 92; epirubicin 120 i.v. days 29, 92; bleomycin 15 i.v. days 43, 106; cytarabine 900 i.v. days 50, 113. Thirty-six outpatients with intermediate- and high-grade non-Hodgkin's lymphomas entered the pilot study; 29 were untreated and 7 had relapse disease. Clinical stage was I in 1 patient, II in 7, III in 5 and IV in 23; 10 had B symptoms; the IPI score was 0-2 in 29 cases and > or =3 in the remaining 7. RESULTS: Of the 29 previously untreated patients, 16 achieved complete remission, 8 partial remission, 4 developed progressive disease and 1 was withdrawn early from the study because of acute viral hepatitis; subsequently 4 relapsed and 3 died (2 of disease progression, 1 of causes unrelated to the disease). In the pre-treated group 3 patients obtained complete remission, 2 partial remission and in 1 patient the disease progressed; 3 of these pre-treated patients died (1 of progressive disease, 1 of a new relapse, 1 of myocardial infarction during therapy). With a 20-month median follow-up, the 30-month overall and relapse-free survival were 0.58 and 0.70, respectively. G-CSF was administered to all but 2 patients, with median delivery throughout the whole regimen of 8, 400 microg per patient. Actual cumulative DI was 0.82+/-0.11. Grade 3-4 hematologic toxicity consisted of anemia in 3 cases, of leukopenia in 8 and of thrombocytopenia in 2; the same grade of non-hematologic toxicity involved the liver in 2 cases, the heart in 1 (the above mentioned death), the digestive mucosa in 2 and the peripheral nerves in 1 patient. INTERPRETATION AND CONCLUSIONS: The iso-DI sequential variant of the ProMACE-CytaBOM regimen can be considered feasibile, relatively non-toxic, and can be given on an out-patient basis. Limited use of G-CSF is required (about 3 vials after each drug administration). Thus, a randomized trial with the original ProMACE-CytaBOM regimen can be designed.

Tumor bulk as a prognostic factor for the management of localized aggressive non-Hodgkin's lymphoma: a survey of the Japan Lymphoma Radiation Therapy Group.

Unique Identifier: 20384655

Author: Oguchi M; Ikeda H; Isobe K; Hirota S; Hasegawa M; Nakamura K; Sasai K; Hayabuchi N

Source: Int J Radiat Oncol Biol Phys 2000 Aug 1;48(1):161-8

Address: Department of Radiology, Shinshu University, School of Medicine, Matsumoto, Japan.

    PURPOSE: To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkin's lymphoma (NHL). METHODS AND MATERIALS: The survey was carried out at 25 radiation oncology institutions in Japan in 1998. The 5-year event-free (EFS) and overall survival rates (OAS) were calculated, and univariate and multivariate analyses were done to identify which of the following factors, namely, gender, age, performance status (PS), serum lactate dehydrogenase (LDH) level, Stage (I vs. II), tumor bulk (maximum diameter), and treatment, were significant from the viewpoint of prognosis. RESULTS: A total of 1141 patients with Stage I and II NHL were treated by the Japanese Lymphoma Radiation Therapy Group between 1988 and 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate- and high-grade lymphomas in working formulation, constituted the core of this study. Primary tumors arose mainly from extranodal organs (71%) in the head and neck (Waldeyer's ring: 36% and sinonasal cavities: 9%). The factors associated with poorer prognosis were age over 60 years old (p < 0. 0001), radiation therapy alone (p < 0.0001), PS = 2-4 (p = 0.0011), (sex male, p = 0.0078), a bulky tumor more than 6 cm in maximum diameter (p = 0.0088), elevated LDH (p = 0.0117), and stage II (p = 0.0642). A median dose of 42 Gy was delivered mainly to the involved fields. Short-course chemotherapy was provided in 549 (70%) patients. The 5-year OAS and EFS rates for all patients were 71% and 67%, respectively. According to the stage-modified International Prognostic Index, the 5-year EFS of the patients with risk factors from 0 to 1 was 76%, 61% for patients with two risk factors, and 26% for patients with three or more risk factors. CONCLUSION: Extranodal presentation, especially Waldeyer's ring and sinonasal cavities, is encountered more frequently in Japan than in Western countries. Tumor bulk is an important prognostic factor in patients with localized aggressive extranodal NHL. Short course chemotherapy followed by radiation therapy was associated with prolonged survival in patients with localized aggressive NHLs of extranodal origin and 0-1 risk factor.

Precursor B-cell lymphoblastic lymphoma in childhood and adolescence: clinical features, treatment, and results in trials NHL-BFM 86 and 90.

Unique Identifier: 20342037

Author: Neth O; Seidemann K; Jansen P; Mann G; Tiemann M; Ludwig WD; Riehm H; Reiter A

Source: Med Pediatr Oncol 2000 Jul;35(1):20-7

Address: Department of Pediatric Hematology and Oncology, Medizinische Hochschule, Hannover, Germany.

    BACKGROUND: Precursor B-cell lymphoblastic lymphoma (PBLL) is a rare subtype of childhood non-Hodgkin lymphoma (NHL). The purpose of our study was to investigate frequency and clinicopathological features of PBLL in children and to test prospectively the efficacy of an ALL-type therapy for treatment of these patients. PROCEDURE: From October, 1986, to March, 1995, 1,075 patients up to 18 years of age suffering from all kinds of NHL were registered in the two consecutive multicenter studies NHL-BFM 86 and 90. Of these, 27 patients were diagnosed with PBLL. Twenty-one PBLL patients were treated according to a BFM-ALL-type protocol: an eight-drug induction over 9 weeks was followed by an 8-week consolidation including methotrexate 5 g/m(2) x4. Patients in stages I and II continued with maintenance up to a total therapy duration of 24 months, whereas patients in stages III and IV received an additional eight-drug intensification and cranial radiotherapy (12 Gy for prophylaxis) after consolidation. Six PBLL patients were treated according to the BFM-protocol for B-NHL, stratified according to stage and tumor load and consisiting of two to six 5-day courses of chemotherapy. RESULTS: The median age of the 27 patients with PBLL (18 boys, 9 girls) was 6.2 (range 0.7-15) years. Stages (St. Jude) were: I (n = 3), II (n = 7), III (n = 9), and IV (n = 8). Twenty-one PBLL patients had nodal disease, 6 patients had subcutaneous manifestations, and 8 patients had bone marrow disease (<25% blasts). All patients achieved remission. With a median follow-up time of 4. 25 years, the estimated probability for event-free survival (pEFS) at 10 years for the total group was 0.73 (SE 0.10). Five patients (2, 1, 1, and 1 patients at stages I, II, III, and IV, respectively) relapsed: 2 of 21 patients who were treated according to the ALL strategy and 3 of 6 who were treated according to the B-NHL-protocol. CONCLUSIONS: PBLL accounts for 2.5% of childhood NHL. An ALL-type therapy strategy appears to be superior to a short-pulse B-NHL protocol. Copyright 2000 Wiley-Liss, Inc.

Improved outcome in childhood B-cell lymphoma with the intensified French LMB protocol.

Unique Identifier: 20342035

Author: Yaniv I; Fischer S; Mor C; Stark B; Goshen Y; Stein J; Cohen IJ; Zaizov R

Source: Med Pediatr Oncol 2000 Jul;35(1):8-12

Address: Institute of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, Beilinson Campus, Petah Tiqva, and Sackler Faculty of Medicine, Tel Aviv University, Israel.

    BACKGROUND: During the last 20 years, 120 children with B cell lymphoma were treated at the National Pediatric Hematology/Oncology Center of Israel. Until 1986, 63 patients received an institutional protocol (BMC), and thereafter 57 patients received a modified French LMB protocol. We report the results of a retrospective analysis comparing the results of these two protocols. PROCEDURE: Patient characteristics were similar in both groups except for stage of disease and lactate dehydrogenase (LDH) levels. Significantly more patients in the LMB group had higher stage disease, and the LDH levels also were higher (<600 microg/ml). RESULTS: Fifty-four of fifty-seven children on the modified LMB protocol are alive, disease-free, with an overall event-free survival of 94% (median follow-up of 73 months). Event-free survival for stages I, II, and III patients is 100%, and for stage IV 77%, whereas the overall event-free survival was 58% among 63 children treated previously, and for stage IV patients only 10%. Severe marrow suppression and neutropenic enterocolitis were the major complications of this intensive protocol. CONCLUSIONS: Intensive chemotherapy with a modified LMB protocol and modern supportive care result in a high cure rate of childhood B cell lymphoma even in patients with advanced disease. Copyright 2000 Wiley-Liss, Inc.

Value of long-term administration of acyclovir and similar agents for protecting against AIDS-related lymphoma: case-control and historical cohort studies [see comments]

Unique Identifier: 20277954

Author: Fong IW; Ho J; Toy C; Lo B; Fong MW

Source: Clin Infect Dis 2000 May;30(5):757-61

Address: Department of Medicine, St. Michael's Hospital, University of Toronto, Ontario, Canada.

    Acyclovir or similar agents with activity against Epstein-Barr virus (EBV) theoretically may prevent non-Hodgkin's lymphoma (NHL) in AIDS. A case-control study of 29 patients with AIDS-related NHL and 58 matched control subjects assessed the frequency with which daily acyclovir (>/=800 mg/d) or similar agents were used for > or =1 year. In a historical cohort of 304 patients with AIDS for > or =2 years, the prevalence of NHL was assessed among 3 groups of patients: those who received long-term treatment with high-dose acyclovir (or similar agents) or low-dose or intermittent acyclovir; those treated with ganciclovir/foscarnet for <1 year; and those who had not previously been treated with acyclovir, ganciclovir, or foscarnet. In the case-control study, 22 patients (72.4%) with NHL never received acyclovir or similar drugs versus 19 control subjects (32.8%; P=. 002); 2 patients (6.9%) with NHL received acyclovir (> or =800 mg/d) for > or =1 year versus 27 (46.6%) of control subjects (P=.0001). In the cohort study, 6 (6.8%) of 88 patients who received acyclovir (> or =800 mg/d) for > or =1 year developed NHL versus 15 (15.5%) of 97 patients who received intermittent or lower-dose acyclovir and 30 (25.2%) of 119 patients who never received these agents (P=.002). Long-term administration (>1 year) of high-dose acyclovir or similar agents with anti-EBV activity may prevent NHL in patients with AIDS. A prospective, randomized study is warranted to confirm these results.

The need for investigations of prophylactic regimens to prevent AIDS-associated non-Hodgkin's lymphoma [editorial; comment]

Unique Identifier: 20277955

Author: Rabkin CS

Source: Clin Infect Dis 2000 May;30(5):762-3

    No abstract available.

Pure red cell aplasia due to parvovirus B19 in a patient treated with rituximab.

Unique Identifier: 20372554

Author: Sharma VR; Fleming DR; Slone SP

Source: Blood 2000 Aug 1;96(3):1184-6

Address: Division of Medical Oncology/Hematology, the Department of Pathology, and the James Graham Brown Cancer Center, University of Louisville, KY 40202, USA.

    Rituximab is a chimeric monoclonal antibody directed against CD20 and used in the treatment of B-cell non-Hodgkin's lymphoma. Due to its ability to deplete B lymphocytes, rituximab can interfere with humoral immunity, causing it to be suppressed for several months after treatment. The reported case depicts a serious consequence of this effect of rituximab therapy: pure red cell aplasia resulting from chronic parvovirus B19 infection. The point of interest in this case is not only the association between rituximab therapy and pure red cell aplasia, but the diagnostic and therapeutic utility of the knowledge of parvovirus B19 as the likely etiologic link between the two. Given the known efficacy of intravenous immunoglobulin (IVIg) in the treatment of chronic parvovirus B19 infection, this therapy can cure some of these patients and successfully render most others transfusion-independent until recovery of their own humoral immune system.

Successful in vivo purging of CD34-containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion.

Unique Identifier: 20372510

Author: Magni M; Di Nicola M; Devizzi L; Matteucci P; Lombardi F; Gandola L; Ravagnani F; Giardini R; Dastoli G; Tarella C; Pileri A; Bonadonna G; Gianni AM

Source: Blood 2000 Aug 1;96(3):864-9

Address: Department of Oncology, University of Milan, Italy.

    Elimination of tumor cells ("purging") from hematopoietic stem cell products is a major goal of bone marrow-supported high-dose cancer chemotherapy. We developed an in vivo purging method capable of providing tumor-free stem cell products from most patients with mantle cell or follicular lymphoma and bone marrow involvement. In a prospective study, 15 patients with CD20(+) mantle cell or follicular lymphoma, bone marrow involvement, and polymerase chain reaction (PCR)-detectable molecular rearrangement received 2 cycles of intensive chemotherapy, each of which was followed by infusion of a growth factor and 2 doses of the anti-CD20 monoclonal antibody rituximab. The role of rituximab was established by comparison with 10 control patients prospectively treated with an identical chemotherapy regimen but no rituximab. The CD34(+) cells harvested from the patients who received both chemotherapy and rituximab were PCR-negative in 93% of cases (versus 40% of controls; P =.007). Aside from providing PCR-negative harvests, the chemoimmunotherapy treatment produced complete clinical and molecular remission in all 14 evaluable patients, including all 6 with mantle cell lymphoma (versus 70% of controls). In vivo purging of hematopoietic progenitor cells can be successfully accomplished in most patients with CD20(+) lymphoma, including mantle cell lymphoma. The results depended on the activity of both chemotherapy and rituximab infusion and provide the proof of principle that in vivo purging is feasible and possibly superior to currently available ex vivo techniques. The high short-term complete-response rate observed suggests the presence of a more-than-additive antilymphoma effect of the chemoimmunotherapy combination used.

Allogeneic bone marrow transplantation for lymphoma.

Unique Identifier: 20263007

Author: Bierman PJ

Source: Blood Rev 2000 Mar;14(1):1-13

Address: University of Nebraska Medical Center, Omaha 68198-7680, USA.

    Registry data show that use of allogeneic transplantation for non-Hodgkin's lymphoma, and to a lesser extent, Hodgkin's disease is increasing. Although no prospective randomized trials have been performed, most comparisons show a significantly lower relapse rate when allogeneic transplant results are compared to results of autologous hematopoietic stem cell transplantation. The lower relapse rate following allogeneic transplantation, as well as several other lines of evidence, support the existence of a graft-versus-lymphoma effect. Nevertheless, in most comparisons, the lower relapse rate following allogeneic transplantation is offset by higher transplant-related mortality. These results make it difficult to find situations where definite overall survival advantages associated with the use of allogeneic transplantation can be demonstrated. The use of low-intensity non-myeloablative regimens for allogeneic transplantation is attracting attention. It is hoped that this approach may harness a graft-versus-lymphoma effect with less morbidity and mortality than conventional allogeneic transplantation, but more data are required to assess the value of this treatment.

Autotransplantation following busulfan, etoposide and cyclophosphamide in patients with non-Hodgkin's lymphoma.

Unique Identifier: 20332137

Author: Copelan EA; Penza SL; Pohlman B; Avalos BR; Goormastic M; Andresen SW; Kalaycio M; Bechtel TP; Scholl MD; Elder PJ; Ezzone SA; O'Donnell LC; Tighe MB; Risley GL; Young DC; Bolwell BJ

Source: Bone Marrow Transplant 2000 Jun;25(12):1243-8

Address: Bone Marrow Transplantation Program, The Ohio State University, Arthur G James Cancer Hospital & Richard J Solove Research Institute, Columbus, Ohio 432110, USA.

    The purpose of the study was to determine the toxicities and effectiveness of a novel preparative regimen of busulfan (Bu) 14 mg/kg, etoposide 50 or 60 mg/kg, and cyclophosphamide (Cy) 120 mg/kg in non-Hodgkin's lymphoma (NHL) and to analyze results using doses based on different body weight parameters and the two different etoposide doses. Three hundred and eighty-two patients aged 16 to 72 underwent first autologous transplantation with mobilized peripheral blood progenitor cells between August 1992 and December 1998 at either of two transplant centers. Mucositis was the most common toxicity. Hepatic toxicity was the most common life-threatening toxicity; severe hepatic VOD occurred in 11 patients (2.9%). Ten patients (2.6%) died from treatment-related toxicity. The 3-year progression-free survival (PFS) for the entire group was 46.9% (95% CI, 40.5-53.3%). Elevated LDH, resistance to chemotherapy, and intermediate/aggressive histology were significant adverse prognostic factors. For patients in sensitive first relapse PFS was 47.0% (95% CI, 37-57%). Neither etoposide dose nor body weight parameter utilized significantly affected outcome. In conclusion, the novel preparative regimen of Bu, etoposide and Cy results in a low incidence of treatment-related mortality and is effective in the treatment of patients with NHL. Bone Marrow Transplantation (2000) 25, 1243-1248.

Successful treatment of relapsed Burkitt's lymphoma using unrelated cord blood transplantation as consolidation therapy.

Unique Identifier: 20332148

Author: Weinthal JA; Goldman SC; Lenarsky C

Source: Bone Marrow Transplant 2000 Jun;25(12):1311-3

Address: Texas Oncology Pediatrics and North Texas Hospital for Children at Medical City Dallas Hospital, Dallas, TX, USA.

    We report a 10-year-old male with widespread recurrent Burkitt's lymphoma who underwent successful mismatched unrelated cord blood transplantation (UCBT) following salvage chemotherapy. He was conditioned with TBI, antithymocyte globulin (ATG) and high-dose VP-16 and achieved full donor engraftment. He experienced grade II skin and grade I gastrointestinal acute GVHD with no chronic GVHD. He is alive with no evidence of disease 24 months following UCBT. Bone Marrow Transplantation (2000) 25, 1311-1313.

Effective high-dose chemotherapy combined with CD34+-selected autologous peripheral blood stem cell transplantation in a patient with cutaneous CD30-negative large T cell lymphoma.

Unique Identifier: 20332149

Author: Nishio M; Koizumi K; Endo T; Takashima H; Haseyama Y; Fujimoto K; Yamamoto S; Kobayashi H; Koike T; Sawada K

Source: Bone Marrow Transplant 2000 Jun;25(12):1315-7

Address: Department of Internal Medicine II, Hokkaido University, School of Medicine, Sapporo, Japan.

    Generalized multiple cutaneous tumors developed in a 60-year-old Japanese man. Skin biopsy revealed atypical large T lymphocytes infiltrating the dermis. CD30 staining was negative in the tumor cells. The diagnosis of CD30-negative cutaneous large T cell lymphoma was made. Axial and inguinal lymphadenopathy was present, but there was no evidence of bone marrow involvement. Seven cycles of chemotherapy and local electron beam irradiation were administered and complete remission (CR) was attained. As CD30-negative cutaneous large T cell lymphoma has a poor prognosis despite intensive chemotherapy, high-dose chemotherapy followed by CD34+-selected autologous peripheral blood stem cell transplantation (CD34+-APBSCT) was prescribed. The clinical course after CD34+-selected APBSCT was complicated with CMV infection occurring twice but administration of ganciclovir resolved the symptoms. He has remained in CR for 16 months after CD34+-APBSCT. This appears to be the first case report of CD34+-APBSCT in a patient with CD30-negative cutaneous large T cell lymphoma. Bone Marrow Transplantation (2000) 25, 1315-1317.

[Initial response to steroids of lung non-Hodgkin's lymphoma (letter)]

Unique Identifier: 20373384

Author: Giron Moreno RM; Gonzalez Ruano P; Losada Molina C

Source: Arch Bronconeumol 2000 May;36(5):292-3

    No abstract available.

The contemporary use of radiation therapy in the management of lymphoma.

Unique Identifier: 20312999

Author: Boyle T; McPadden E

Source: Surg Oncol Clin N Am 2000 Jul;9(3):621-37, xi

Address: Department of Radiation Oncology, New England Medical Center, Tufts University School of Medicine, Boston, MA, USA.

    In this article the classification and the treatment regimens for malignant lymphomas are discussed in a stage-oriented approach. The clinical trials that have redefined the role of staging laparotomy are reviewed. Intensity-modulated radiation therapy allows for highly conformal target definition. This novel delivery system is discussed through a case presentation.

High dose therapy and autologous stem cell transplantation for human immunodeficiency virus-associated non-Hodgkin lymphoma in the era of highly active antiretroviral therapy.

Unique Identifier: 20389464

Author: Molina A; Krishnan AY; Nademanee A; Zabner R; Sniecinski I; Zaia J; Forman SJ

Source: Cancer 2000 Aug 1;89(3):680-9

Address: Division of Hematology and Bone Marrow Transplantation, City of Hope National Medical Center, Duarte, California 91010, USA.

    BACKGROUND: The advent of highly active antiretroviral therapy (HAART) has allowed the exploration of more dose-intensive therapy such as autologous stem cell transplantation (ASCT) in selected patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL). METHODS: The authors report on the use of myeloablative chemotherapy with ASCT in two HIV positive patients with NHL. The first patient underwent ASCT at the time of first disease remission for poor risk, diffuse, large cell NHL and the second patient had multiply recurrent, chemosensitive Burkitt lymphoma. ASCT was performed in both patients using a transplant conditioning regimen of high dose cyclophosphamide, carmustine, and etoposide (CBV). RESULTS: The target dose of >/= 5 x 10(6)/kg CD34 positive peripheral blood stem cells (PBSC) utilized for ASCT was collected using granulocyte-colony stimulating factor (G-CSF) after chemotherapy for mobilization while both patients were receiving concomitant HAART for HIV infection. HAART was continued during CBV conditioning. Prompt hematopoietic recovery was observed after ASCT. Both patients remained in clinical disease remission from their lymphoma at 28 months and 20 months after transplant, respectively. CONCLUSIONS: ASCT is feasible in patients with HIV-associated NHL. Adequate numbers of CD34 positive PBSC can be procured from patients receiving HAART and chemotherapy for NHL. Selected patients with HIV-related lymphoma can tolerate the high dose CBV myeloablative chemotherapy regimen without increased acute regimen-related toxicity. Reinfusion of G-CSF-mobilized PBSC can lead to rapid recovery of hematologic function and sustained engraftment after ASCT. Given the poor prognosis of patients with HIV-associated NHL treated with conventional chemotherapy, further investigation of this approach should be considered. Copyright 2000 American Cancer Society.

Intracardiac lymphoma in a child: successful treatment with chemotherapy alone.

Unique Identifier: 20325459

Author: Agarwala B; Rubin CM

Source: Pediatr Cardiol 2000 Jul-Aug;21(4):401-2

Address: Department of Pediatrics, University of Chicago Children's Hospital, 5839 S. Maryland Avenue, Chicago, IL 60637, USA.

    A 5-year-old female child with history of non-Hodgkin's lymphoma presented with cough and palpitation. On physical examination a cardiac tumor plop was heard. Paroxysmal supraventricular tachycardia was noted on the electrocardiogram. Transthoracic echocardiogram revealed multiple large tumor masses within the right and the left atrium. The right atrial tumor was flopping back and forth at the tricuspid valve orifice. The tumor resolved completely with chemotherapy without any surgical intervention.

[Genetic analysis after allograft: prudence! (letter)]

Unique Identifier: 20394604

Author: Billon S; Mercier B; Ferec C; Abgrall JF

Source: Presse Med 2000 Jul 8-15;29(24):1353

    No abstract available.

Acquired immunodeficiency syndrome-related primary cerebral lymphoma: response to irradiation.

Unique Identifier: 20308527

Author: Khoo VS; Wilson PC; Sexton MJ; Liew KH

Source: Australas Radiol 2000 May;44(2):178-84

Address: Academic Unit of Clinical Oncology, Royal Marsden NHS Trust, Sutton, Surrey, United Kingdom.

    Acquired immunodeficiency syndrome-related primary cerebral lymphoma (AIDS-PCL) is uncommon. Fourteen cases of presumed AIDS-PCL between 1986 and 1995 were reviewed retrospectively in order to characterize the natural history, and the response to radiotherapy. The median age was 38 years (range 24-65). The median interval between seropositive diagnosis of HIV and AIDS-PCL was 28 months (range 5-113). The median duration of symptoms was 2 weeks (range 0.2-12). At presentation, the Eastern Cooperative Oncology Group performance status (PS) was PS1 (2/14 patients), PS2 (6/14) and PS3 (6/14). The symptoms and signs were non-specific and depended on the site and extent of cerebral involvement. There was no characteristic pattern of brain imaging in terms of size, number, location or pattern of contrast enhancement of the cerebral lesions. Nine patients received various fractionation-dose schedules (range 8-50 Gy). Complete and partial responses were seen in 2/9 and 3/9 cases, respectively. Clinical stabilization of neurological symptoms was noted in 3/9 cases and disease progression in 1/9. The median survival times (MST) from presentation for irradiated and non-irradiated patients were 9.3 and 2.1 weeks, respectively (range 0.9-43.1). Although patient selection introduced bias, there appears to be a modest improvement in MST for treated patients. The MST with radiotherapy alone remains poor, but radiotherapy may provide palliation. For some selected patients, a prolonged response is possible.

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