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In order to study efficacy, toxicity and the long-term results of donor lymphocyte infusions (DLI), we retrospectively analyzed DLI given for relapse after conventional allogeneic hematopoietic stem cell transplantation (HSCT) in 30 patients with a median delay of 107.5 months after transplant and 58 months after DLI. After DLI, 15 patients established full donor chimerism, three patients developed grade III and one grade IV acute GVHD. A total of 15 patients achieved a disease response. Among the 14 patients with chronic myeloid leukemia (CML), 11 are alive at the last follow-up: five are in complete molecular response (CMR) and two in complete cytogenetic response (CCR) with no other intervention after DLI, three in CMR after imatinib mesylate given after DLI and one in complete hematological response after imatinib mesylate and reduced-intensity conditioning allogeneic SCT performed after DLI. At the time of the last follow-up, 19 (63%) patients died and 11 (37%) remain alive. The 3-year probability of survival for the entire population, CML patients and non-CML patients, was 60, 93, 62% after transplantation, and 48, 80 and 48% after DLI, respectively. A multivariate analysis demonstrated a significantly worse survival rate after transplantation for female recipients, advanced disease and acute leukemia before transplantation.

Objectives: To analyze the consequences of lymphocyte donations on lymphopoiesis in donors having previously undergone hematopoietic stem cell collection for allogeneic stem cell transplantation., Methods: Repeated analysis of leukocyte subsets in the peripheral blood of 76 hematopoietic stem cell donors undergoing lymphocyte donation(s) for DLI., Results: Grade I/II lymphopenia was present in 22 donors (29%) just before first apheresis for lymphocyte collection, demonstrating that former stem cell donation induced prolonged lymphopenia in a subset of donors. The monocytic lineage was not affected. Older age and history of PBSC harvest constituted 2 independent factors of lymphopenia, but had no influence on monocytopenia. The first apheresis induced lymphopenia in 36 donors (47%) and monocytopenia in 23 donors (39%). Lymphopenia before first apheresis and prior history of PBSC harvest were independent factors of apheresis-induced lymphopenia while those factors had no influence on monocytopenia. A time-dependent decrease in lymphocyte counts was observed in donors undergoing repeated aphereses, resulting in persistent and prolonged lymphopenia in 50% of donors. No persistent monocytopenia over time and aphereses was observed. Kaplan-Meier estimate of the risk to develop persistent lymphopenia after multiple aphereses was 21% +/- 6% at 2 months, 38% +/- 8% at 4 months, and 64% +/- 10% at 12 months. After Cox regression analysis, previous PBSC harvest remained the unique factor associated with the risk for persistent lymphopenia., Conclusions: Monitoring the potential long-term effects of repeated aphereses in hematopoietic stem cell donors appears important. Selecting young bone marrow donors for subsequent DLI significantly reduces the risk for acute and prolonged lymphopenias.

Peripheral blood stem cells (PBSC) from 15 patients with advanced non-Hodgkin's lymphoma (NHL), two patients with chronic lymphocytic leukemia, and two patients with myeloma were collected by continuous-flow leukapheresis after chemotherapy with MIV (mitoxantrone, ifosfamide, and etoposide, five patients) or high-dose cyclophosphamide (14 patients), followed by administration of GM-CSF. Sixteen patients (84%) had persistent marrow involvement at time of inclusion. Results were compared to those obtained in a control group of similar age and disease status in whom collection had been performed after MIV chemotherapy alone. The number of mononuclear cells, granulocyte-macrophage colony-forming units (CFU-GM), CD34+ cells were higher in GM-CSF treated patients with a lower mean number of leukapheresis (3.5 versus 6.4). Among the 19 patients harvested after chemotherapy plus GM-CSF, more progenitor cells were obtained in the cyclophosphamide group than in the MIV group. In all these patients except one, the number of mononuclear cells was sufficient to realize a transplantation. Seventeen patients received intensification with BEAM regimen (8 patients) or cyclophosphamide plus etoposide and total body irradiation (9 patients). Two patients failed to reconstitute correct hematopoiesis and three early toxic deaths occurred for a total of five procedure-related deaths. Nine of these 17 patients are in persistent complete remission with a median post-transplant follow-up of 18 months. Time to reach granulocyte and platelet recovery was not correlated with the number of mononuclear cells, CFU-GM, granulocyte-erythroid-macrophage-megakaryocyte colony-forming units (CFU-GEMM), CD34+ cells, and CD34+ CD33- cells but with the number of previous chemotherapy regimens. PBSC harvesting is achievable after chemotherapy plus GM-CSF in heavily pretreated patients with persistent marrow involvement. Moreover, these cells are able to reconstitute correct hematopoiesis after intensive treatment in these patients.

A 22-year-old woman had an idiopathic pure red cell aplasia that failed to respond to high doses of corticosteroids. After a series of 10 plasma exchange procedures, bone marrow erythropoiesis and reticulocyte blood count returned to normal; the haematological remission has been now persistent for 12 months. The place of plasma exchange in the management of pure red cell aplasia and its mode of action will be discussed.