Graft-Versus-Lymphoma Effect of Donor Leukocyte Infusion in Indolent Lymphomas Relapsed after T-Cell Depleted Allogeneic Stem Cell Transplantation, Substantiated by Real-Time PCR Quantitation and Immunophenotyping.

Caroline Mandigers, Leo Verdonck, Jules Meijerink, Anton Schattenberg, Evelyn Tonnissen, John Raemaekers.

Author address: 

Hematology, University Medical Center, Nijmegen, Netherlands; Hematology, University Medical Center, Utrecht, Netherlands; Central Hematology Laboratory, University Medical Center, Nijmegen, Netherlands

Abstract: 

In case of relapsed hematologic disease after allogeneic stem cell transplantation (SCT) remission can still be induced by infusion of leukocytes derived from the original stem cell donor (DLI). Data on the effect of DLI in relapsed indolent lymphomas are rather scarce. We treated 7 patients with DLI for relapse of indolent non-Hodgkin's lymphoma (NHL) after T-cell depleted SCT. In available bone marrow and blood samples lymphoma cells were analyzed by real-time quantitative polymerase chain reaction of t(14;18) positive cells in follicular NHL, and by immunophenotyping in small lymphocytic NHL. The original pathological diagnoses before SCT were follicular NHL (n=5) and small lymphocytic NHL (n=2) of low grade malignancy. 2/7 Patients had chemotherapy-refractory disease prior to SCT. The median age of patients at the time of SCT was 48 years (range 32-56). After conditioning with cyclophosphamide and total body irradiation (n=4), or with additional idarubicin (n=3) stem cells from genetic identical sibling donors were infused. After SCT neither acute graft-versus-host disease (GVHD) grade 3 was seen, nor extensive chronic GVHD. The relapses were diagnosed at a median of 25 (range 12-73) months after SCT and were localized at previously involved lymph nodes and bone marrow. DLI consisted of median 0.9 (range 0.1-1.0) x10*8 CD3+ cells per kg body weight. Three patients were treated with DLI as sole therapy and reached a complete remission; no acute GVHD and only limited chronic GVHD were seen in these patients. The other four patients received additional therapy before DLI. Three of them were treated with chemo- and/or radiotherapy, and one with anti-CD20 (rituximab). 3/4 Patients reached a partial remission and 1/4 a complete remission. In these four patients neither acute GVHD grade 3 was seen, nor extensive chronic GVHD. Up to now five patients are in continuing complete remission for a median of 23 (range 1-66) months. Two patients died 2 and 17 months after DLI of aspergillus fumigatus pneumonia and of liver failure of unknown cause without signs of active NHL respectively. Clinical complete remissions could be substantiated by correlating quantitave molecular analysis of t(14;18)+ cells in 2 relapsed follicular NHL. In one t(14;18)+ cells decreased from 6.512/75.000 cells prior to DLI to 0 after DLI in the peripheral blood and from 3.409/75.000 cells prior to DLI to 0 after DLI in the bone marrow. In the other patient circulating t(14;18)+ cells decreased from pre-DLI 39/75.000 cells to 0 post-DLI. In the other follicular lymphoma patients no t(14;18)+ cells could be demonstrated in pretreatment blood/BM samples thereby precluding monitoring numbers of t(14;18)+ cells. Immunophenotyping of blood and bone marrow in one of the relapsed small lymphocytic lymphoma patients showed disappearance of the CD5+ CD19+ clone after DLI, corresponding with the clinically observed complete remission. DLI is effective treatment for relapsed indolent lymphoma after T-cell depleted SCT.
2001

abstract No: 

NULL

Full conference title: 

43rd American Society of Hematology (ASH) Annual Meeting
    • ASH 43rd (2001)