Autologous Versus Allogeneic Bone Marrow Transplantation for Non-Hodgkin's Lymphoma: A Case-Controlled Analysis of the European Bone Marrow Transplant Group Registry Data By R. Chopra, A.H. Goldstone, R. Pearce, T. Philip, F. Petersen, F. Appelbaum, E. De Vol, and P. Ernst Purpose: A case-controlled study of patients who reported to the European Bone Marrow Transplant Group (EBMTG) was performed to investigate the relative roles and efficacy of allogeneic (alloBMT) and autologous bone marrow transplantation (ABMT) in non-Hodgkin's lymphoma. Patients and Methods: Of 1,060 patients who reported to the lymphoma registry, 938 patients underwent ABMT and 122 patients underwent alloBMT. A casecontrolled study was performed by matching 101 alloBMT patients with 101 ABMT patients. The case matching was performed after the selection of the main prognostic factors for progression-free survival by a multivariate analysis. Results: The progression-free survival was similar in both types of transplants (49% alloBMT v 46%ABMT). The overall relapse and progression rate for the alloBMT patients was 23% compared with 38% in the ABMT patients. This difference was not significant statistically. In

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PRIMARY CONVENTIONAL chemotherapy has failed for non-Hodgkin's lymphoma (NHL), one potentially curative approach is high-dose chemoradiotherapy and bone marrow rescue.1,2 In some cases of advanced NHL, such as adult stage IV Burkitt's and adult lymphoblastic lymphoma, the overall survival with conventional front-line acute lymphoblastic leukemia (ALL) type of chemotherapy may even be 20% or less.3, 4 For such patients, it may be justifiable to consolidate chemotherapy with high-dose chemoradiotherapy and bone marrow transplantation (BMT) in first remission. Although the clinical indications for dose escalation in NHL are now more clearly defined, 5 issues such as the optimal source of bone marrow and type of conditioning regimen remain unresolved. Autologous

From the Department of Hematology, University College and Middlesex School of Medicine, London; Clinical Operational Research Unit, University College, London, United Kingdom; Centre Leon Berard,Lyons, France;FredHutchinson Cancer Center, Seattle, WA; and KingFaisalSpecialistHospitaland Research Center, Riyadh, SaudiArabia. SubmittedApril 9, 1992; acceptedJuly 9, 1992. R.C. was supported by the Leukaemia Research Fund of Great Britain. Address reprint requests to A.H. Goldstone, MD, Department of Hematology, University College Hospital, London, WCIE 6AU, United Kingdom. C 1992 by American Society of Clinical Oncology. 0732-183X/92/1011-0006$3.00/0

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the lymphoblastic lymphoma subgroup, alloBMT was associated with a lower relapse rate than ABMT (24% alloBMT v 48% ABMT; P = .035). The progression-free survival, however, was not significantly different because patients with lymphoblastic lymphoma who underwent alloBMT had a higher procedure-related mortality (24% alloBMT v 10% ABMT; P = .06). A significantly lower relapse/progression rate was also observed in patients with chronic graft-versus-host disease (cGVHD) compared with those patients without (0% cGVHD v 35% no cGVHD; P = .02). Fourteen of 18 patients who had cGVHD also had lymphoblastic lymphoma. Conclusion: This study suggests that ABMT and alloBMT for non-Hodgkin's lymphoma are comparable, with the exception of lymphoblastic lymphoma in which a graftversus-lymphoma effect may account for the lower relapse rate for patients who underwent alloBMT. J Clin Oncol 10: 1690-1695. © 1992 by American Society of ClinicalOncology. bone marrow rescue has been used in more than 1,000 of these patients worldwide, but the reports of the use of allogeneic bone marrow from a matched sibling donor are limited.6-1° By August 1990, there had been 938 patients with NHL reported to the European Bone Marrow Transplant Group (EBMTG) registry for autologous BMT (ABMT) in lymphoma, and only 122 patients reported to the allogeneic BMT (alloBMT) registry. The comparison of ABMT and alloBMT registry data is difficult because of the disparity between the groups, particularly in terms of the selection biases of the reporting centers. The differences between the groups are compounded by the specific circumstances in which either ABMT or alloBMT is not possible. ABMT may not be feasible because of persistent marrow involvement or inadequate marrow reserve as a result of prior cytotoxic chemotherapy or irradiation. On the other hand, alloBMT may not be possible because of the lack of an human leukocyte antigen (HLA)-matched sibling donor or because of the increased risk of procedurerelated mortality from graft-versus-host disease (GVHD) with age." There is undoubtedly a tendency not to allograft older patients even if a donor is available. Any comparison between ABMT and alloBMT patients from the registry must attempt to control for these differences. We have undertaken a case-controlled study of the two groups of patients and have reported the results

Journalof Clinical Oncology, Vol 10, No 11 (November), 1992: pp 1690-1695

Downloaded from ascopubs.org by UNIVERSITY LIVERPOOL on April 20, 2019 from 154.059.124.102 Copyright © 2019 American Society of Clinical Oncology. All rights reserved.

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ABMT v ALLOBMT FOR NON-HODGKIN'S LYMPHOMA on 202 patients who were matched from a data base of 1,060 patients. PATIENTS AND METHODS Definitions Progression-free survival (PFS) was measured in months and was defined as the time from the day of transplantation until disease relapse/progression or death from any cause. This parameter gives the best indication of the efficacy of treatment in lymphoma patients because residual masses on conventional imaging may not necessarily represent active disease. Relapse and progression was defined as disease progression with deaths from procedure-related mortality being censored. Patients with disease that showed a partial response (PR) to conventional-dose salvage chemotherapy were considered to be a responding relapse (RESP REL), and those with no response to such treatment were deemed as resistant relapse (RESIS REL). Patients who had achieved a greater than 75% response to initial therapy were considered as very good partial responders (VGPR). Those who had achieved a less than 75% response to initial therapy were deemed as a primary refractory. Patients who had received no conventional salvage treatment on relapse but proceeded to ABMT were classified as an untreated relapse.

Patient Selection and Characteristics We examined the data of 938 NHL patients who underwent ABMT and 122 patients who underwent alloBMT. All patients were reported to the EBMTG lymphoma registry. The characteristics and diagnoses of these patients are listed in Table 1. A form of multivariate analysis, proportional hazards regression modeling,12 was used to determine the main prognostic factors for both the patients who underwent ABMT and alloBMT. In this approach, the most significant prognostic factor is first identified and a regression fit found. The remaining candidate factors are then inspected to find the one whose inclusion in the regression model gives the most significant improvement in the regression fit. Thus, the factors found to be significant are those that have a significant effect that is independent of the other significant

Table 1. Patient Characteristics From EBMTG Registry ABMT (n = 938) No.

Males Females Age, years Range TBI Chemotherapy only BL. LBL Intermediate/high grade Low grade

612 326

%

65 35

34 1-60 384 40

AllIoBMT (n = 122)* No.

%

P

84 38

68 32

NS NS .02

23 1-40

113

92

.01

519 103 216

55 11 23

9 11 55

8 9 45

Autologous versus allogeneic bone marrow transplantation for non-Hodgkin's lymphoma: a case-controlled analysis of the European Bone Marrow Transplant Group Registry data.

A case-controlled study of patients who reported to the European Bone Marrow Transplant Group (EBMTG) was performed to investigate the relative roles ...
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