High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission.

PURPOSE The role for high-dose therapy and autologous stem-cell transplantation in mantle-cell lymphoma (MCL) is unknown. We retrospectively analyzed patients with chemosensitive disease who underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) for MCL in first remission, as well as following relapse from conventional therapy. PATIENTS AND METHODS Between August 1985 and April 1996, 28 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total-body irradiation (TBI) and a bone marrow-purging regimen. Re-review of original tissue demonstrated that all patients had morphologic, phenotypic, and genotypic characteristics of MCL. MCL was the original diagnosis in 21 patients, whereas seven patients had a prior diagnosis of diffuse small cleaved-cell lymphoma. RESULTS Twenty patients received multiple regimens before ABMT, while eight underwent ABMT in first complete remission (CR)/partial remission (PR) following CHOP induction. At bone marrow harvest, only 18% of patients were in CR and overt BM infiltration was present in 57%. Following cyclophosphamide/TBI, no treatment-related deaths were seen. Nineteen of 28 patients have relapsed at a median time of 21 months (range, 3 to 70). Of eight patients transplanted in first CR/PR, five have relapsed. Nine patients are in continuous CR with a median follow-up time of 24 months (range, 10 to 135). Disease-free survival (DFS) and overall survival (OS) are estimated to be 31% and 62% at 4 years, respectively. CONCLUSION ABMT using cyclophosphamide/TBI conditioning may at best be effective in only a small fraction of patients with relapsed MCL. The lack of plateau with a median follow-up time of 24 months suggests cure may not be achievable. The role of this therapy in patients in first remission requires more study using better induction therapy to enhance the CR rate before ABMT.

[1]  J. Gribben,et al.  High-dose therapy and autologous bone marrow transplantation in patients with follicular lymphoma during first remission. , 1996, Blood.

[2]  G. Inghirami,et al.  Large‐cell variants of mantle cell lymphoma: cytologic characteristics and p53 anomalies may predict poor outcome , 1996, British journal of haematology.

[3]  E. Noordijk,et al.  Mantle-cell lymphoma: a population-based clinical study. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  A. Hagenbeek,et al.  Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. , 1995, The New England journal of medicine.

[5]  A. Hagenbeek,et al.  Efficacy of four different regimens in 64 mantle-cell lymphoma cases: clinicopathologic comparison with 498 other non-Hodgkin's lymphoma subtypes. European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  I. Bernstein,et al.  Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas , 1995, The Lancet.

[7]  B. Nathwani,et al.  A clinical analysis of two indolent lymphoma entities: mantle cell lymphoma and marginal zone lymphoma (including the mucosa-associated lymphoid tissue and monocytoid B-cell subcategories): a Southwest Oncology Group study. , 1995, Blood.

[8]  H Stein,et al.  A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. , 1994, Blood.

[9]  J. Gribben,et al.  Detection of residual lymphoma cells by polymerase chain reaction in peripheral blood is significantly less predictive for relapse than detection in bone marrow , 1994 .

[10]  G. Salles,et al.  Nonfollicular small B-cell lymphomas: a heterogeneous group of patients with distinct clinical features and outcome. , 1994, Blood.

[11]  F. Berger,et al.  Detection of the chromosomal translocation t(11;14) by polymerase chain reaction in mantle cell lymphomas. , 1994, Blood.

[12]  F. Cavalli,et al.  Treatment and prognosis of centrocytic (mantle cell) lymphoma: a retrospective analysis of twenty-six patients treated in one institution. , 1994, Leukemia & lymphoma.

[13]  I. Bernstein,et al.  Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. , 1993, The New England journal of medicine.

[14]  M. Williams,et al.  Chromosome t(11;14)(q13;q32) breakpoints in centrocytic lymphoma are highly localized at the bcl-1 major translocation cluster. , 1993, Leukemia.

[15]  J. Gribben,et al.  Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma. , 1993, Blood.

[16]  D. Neuberg,et al.  Autologous bone marrow transplantation in poor-prognosis intermediate-grade and high-grade B-cell non-Hodgkin's lymphoma in first remission: a pilot study. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  G. Pinkus,et al.  Intermediate lymphocytic lymphoma: clinical and pathologic features of a recently characterized subtype of non-Hodgkin's lymphoma. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  J. Gribben,et al.  Bone marrows of non-Hodgkin's lymphoma patients with a bcl-2 translocation can be purged of polymerase chain reaction-detectable lymphoma cells using monoclonal antibodies and immunomagnetic bead depletion. , 1992, Blood.

[19]  T. Grogan,et al.  Diffuse small cleaved-cell lymphoma: a heterogeneous disease with distinct immunobiologic subsets. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  S. Pileri,et al.  Mantle Cell Lymphoma. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  J. Gribben,et al.  All advanced stage non-Hodgkin's lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment. , 1991, Blood.

[22]  J. Gribben,et al.  Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. , 1991, The New England journal of medicine.

[23]  D. Weisenburger,et al.  Diffuse intermediate lymphocytic lymphoma. A clinicopathologic study and comparison with small lymphocytic lymphoma and diffuse small cleaved cell lymphoma , 1990, Cancer.

[24]  D. Weisenburger,et al.  Mantle zone lymphoma a clinicopathologic study of 22 cases , 1990, Cancer.

[25]  E. Jaffe,et al.  Lymphocytic lymphoma of intermediate differentiation: morphologic, immunophenotypic, and prognostic factors. , 1990, Journal of the National Cancer Institute.

[26]  B. Yeap,et al.  Autologous bone marrow transplantation in B-cell non-Hodgkin's lymphoma: very low treatment-related mortality in 100 patients in sensitive relapse. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  H. Lazarus,et al.  The Treatment of Progressive Non-Hodgkin's Lymphoma With Intensive Chemoradiotherapy and Autologous Marrow Transplantation , 1990 .

[28]  M. Engelhard,et al.  Multicentre randomized therapeutic trial for advanced centrocytic lymphoma: Anthracycline does not improve the prognosis , 1989, Hematological oncology.

[29]  J. Armitage,et al.  High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. , 1987, The New England journal of medicine.

[30]  S. Horning,et al.  The natural history of initially untreated low-grade non-Hodgkin's lymphomas. , 1984, The New England journal of medicine.

[31]  T. Lister,et al.  Centrocytic lymphoma: a distinct clinicopathologic and immunologic entity. A multiparameter study of 18 cases at diagnosis and relapse. , 1983, The American journal of pathology.

[32]  D. Weisenburger,et al.  Mantle‐zone lymphoma: A follicular variant of intermediate lymphocytic lymphoma , 1982, Cancer.

[33]  N. Mantel Evaluation of survival data and two new rank order statistics arising in its consideration. , 1966, Cancer chemotherapy reports.

[34]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[35]  D. Weisenburger,et al.  Intermediate lymphocytic lymphoma: immunophenotypic and cytogenetic findings. , 1987, Blood.