Journal of Clinical Oncology, Vol 12, 1685-1692, Copyright © 1994 by American Society of Clinical Oncology

ARTICLES

Sequential high-dose therapy with peripheral-blood progenitor-cell support in low-grade non-Hodgkin's lymphoma

R Haas, M Moos, A Karcher, R Mohle, B Witt, H Goldschmidt, S Fruhauf, M Flentje, M Wannenmacher and W Hunstein
Department of Internal Medicine V, University of Heidelberg, Germany.

PURPOSE: To evaluate the feasibility of a sequential high-dose therapy with peripheral-blood progenitor-cell (PBPC) support in patients with follicular lymphoma. PATIENTS AND METHODS: Since July 1991, we have included 30 patients (17 men and 13 women) with a median age of 41 years (range, 26 to 55) in the study. At the time of study entry, 17 patients were in first and six in second or higher remission. Another six patients had relapse of disease and one had tumor progression. PBPC were collected during filgrastim-supported leukocyte recovery following high-dose cytarabine (ara-C)/mitoxantrone (HAM). RESULTS: A median of two leukaphereses (range, one to seven) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 2.9 to 23.7 x 10(6). A distinct population of B-lymphoid progenitors (CD34+/CD19+) was not detectable in the autografts, and the content of CD19+ B cells was remarkably low, comprising a median of 0.07% of the mononuclear cells. Using the polymerase chain reaction (PCR) assay for the major breakpoint regions (MBR) of the bcl-2/immunoglobulin H (IgH) translocation, 22 patients had autografts positive for the t(14;18) translocation, whereas seven patients had PCR-negative transplants. The autograft of one patient could not be assessed. Following myeloablative therapy, hematologic recovery was rapid without cytokine support. The median times to reach a platelet count > or = 20 x 10(9)/L and neutrophil count > or = 0.5 x 10(9)/L were 11 and 13 days, respectively. Nonhematologic toxicity was moderate. Twenty-nine patients were alive in remission after a median follow-up duration of 6 months (range, 1 to 18). Of 22 patients autografted with t(14;18)-positive harvests, 11 had PCR-detectable cells in bone marrow and/or peripheral blood as long as 16 months posttransplantation. In contrast, six patients became PCR-negative between 3 and 16 months after reinfusion. Follow-up examinations with PCR data for the remaining five patients are not yet available. CONCLUSION: Conversion to PCR negativity in patients autografted with PCR-positive harvests suggests that the myeloablative regimen is effective and that any reinfused t(14;18)-positive cells may not be sustained. Because conventional chemotherapy provides no cure, we believe that high-dose therapy including total-body irradiation (TBI) should be explored in these particularly radiosensitive lymphomas.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. Kornacker, J. Stumm, C. Pott, S. Dietrich, S. Sussmilch, M. Hensel, M. Nickelsen, M. Witzens-Harig, M. Kneba, N. Schmitz, et al. Characteristics of relapse after autologous stem-cell transplantation for follicular lymphoma: a long-term follow-up Ann. Onc., April 1, 2009; 20(4): 722 - 728. [Abstract] [Full Text] [PDF]

				C. Sebban, P. Brice, R. Delarue, C. Haioun, B. Souleau, N. Mounier, N. Brousse, P. Feugier, H. Tilly, P. Solal-Celigny, et al. Impact of Rituximab and/or High-Dose Therapy With Autotransplant at Time of Relapse in Patients With Follicular Lymphoma: A GELA Study J. Clin. Oncol., July 20, 2008; 26(21): 3614 - 3620. [Abstract] [Full Text] [PDF]

				P. Corradini, M. Ladetto, F. Zallio, M. Astolfi, E. Rizzo, S. Sametti, A. Cuttica, R. Rosato, L. Farina, M. Boccadoro, et al. Long-Term Follow-Up of Indolent Lymphoma Patients Treated With High-Dose Sequential Chemotherapy and Autografting: Evidence That Durable Molecular and Clinical Remission Frequently Can Be Attained Only in Follicular Subtypes J. Clin. Oncol., April 15, 2004; 22(8): 1460 - 1468. [Abstract] [Full Text] [PDF]

				H. C. Schouten, W. Qian, S. Kvaloy, A. Porcellini, H. Hagberg, H. E. Johnsen, J. K. Doorduijn, M. R. Sydes, and G. Kvalheim High-Dose Therapy Improves Progression-Free Survival and Survival in Relapsed Follicular Non-Hodgkin's Lymphoma: Results From the Randomized European CUP Trial J. Clin. Oncol., November 1, 2003; 21(21): 3918 - 3927. [Abstract] [Full Text] [PDF]

				J. Apostolidis, R. K. Gupta, D. Grenzelias, P. W. M. Johnson, V. I. Pappa, K. E. Summers, A. Salam, K. Adams, A. J. Norton, J. A. L. Amess, et al. High-Dose Therapy With Autologous Bone Marrow Support as Consolidation of Remission in Follicular Lymphoma: Long-Term Clinical and Molecular Follow-Up J. Clin. Oncol., February 1, 2000; 18(3): 527 - 527. [Abstract] [Full Text] [PDF]

				J. Apostolidis, J. M. Foran, P.W.M. Johnson, A. Norton, J. Amess, J. Matthews, M. Bradburn, T.A. Lister, and A. Z.S. Rohatiner Patterns of Outcome Following Recurrence After Myeloablative Therapy With Autologous Bone Marrow Transplantation for Follicular Lymphoma J. Clin. Oncol., January 1, 1999; 17(1): 216 - 216. [Abstract] [Full Text] [PDF]

				M. T. Voso, S. Hohaus, M. Moos, and R. Haas Lack of t(14; 18) Polymerase Chain Reaction-Positive Cells in Highly Purified CD34+ Cells and Their CD19 Subsets in Patients With Follicular Lymphoma Blood, May 15, 1997; 89(10): 3763 - 3768. [Abstract] [Full Text] [PDF]

				M. Mielcarek, P. J. Martin, and B. Torok-Storb Suppression of Alloantigen-Induced T-Cell Proliferation by CD14+ Cells Derived From Granulocyte Colony-Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells Blood, March 1, 1997; 89(5): 1629 - 1634. [Abstract] [Full Text] [PDF]

				P. Corradini, M. Astolfi, C. Cherasco, M. Ladetto, C. Voena, D. Caracciolo, A. Pileri, and C. Tarella Molecular Monitoring of Minimal Residual Disease in Follicular and Mantle Cell Non-Hodgkin's Lymphomas Treated With High-Dose Chemotherapy and Peripheral Blood Progenitor Cell Autografting Blood, January 15, 1997; 89(2): 724 - 491. [Abstract] [Full Text] [PDF]