Engraftment was achieved in 43/45 (95%) recipients of peripheral blood stem cells (PBSC) from HLA-compatible unrelated donors (n = 45), compared to all 45 patients in matched controls receiving bone marrow and 14/18 (78%) recipients of CD34-selected PBSC (P < 0.01). The time to reach ANC >0.5 x 10(9)/l was a median of 16 days in the PBSC and CD34 groups, compared to 20 days in the bone marrow controls (P < 0.001 vs PBSC). The time to reach platelets >50 x 10(9)/l was a median of 23 days in the PBSC group and 24 days in the CD34 group, which was significantly faster than 29 days in the bone marrow controls (P < 0.01). Acute GVHD grades II-IV developed in 30% in the PBSC group, 20% in the recipients of bone marrow and 18% in the CD34 group. The corresponding figures for chronic GVHD were 59%, 85% and 0% (P < 0.01) in the three groups, respectively. The probability of non-relapse death was 27% in the recipients of PBSC, 21% in the bone marrow controls and 60% in the CD34 group (NS). The 2-year leukaemia-free survival was 46% in the PBSC group, 41% in the bone marrow group and 25% in the CD34 group (NS).
Summary:We report 27 patients with relapsed acute or chronic leukemia who underwent a second hematopoietic stem cell transplant (HSCT) from a related or unrelated donor. Seventeen patients were diagnosed with acute myelogenous leukemia (AML), six with acute lymphocytic leukemia (ALL) and four with chronic myeloid leukemia (CML). Ages ranged from 22 to 49 years (median 37); 13 patients were female and 14 male. Relapse was diagnosed between 1 and 45 months after the first HSCT. Sixteen patients who relapsed had received an autologous transplant initially and 11 an allogeneic transplant. Ten patients relapsed within 6 months and 17 patients later than 6 months. Chemotherapy was used as reinduction for relapse after HSCT in 16 patients who had received an autologous transplant and in three who had received an allogeneic transplant, since the latter did not respond to reduction of immunosuppression to induce a graft-versus-leukemia (GVL) reaction. Five of these 19 patients (26%) achieved complete remission (CR), seven patients did not respond to chemotherapy and seven achieved a partial remission (PR). The stem cell source for the second HSCT included bone marrow (n = 12) and PBSC (n = 4) from genotypically identical unrelated donors, PBSC (n = 7) and bone marrow (n = 3) from related donors. Currently eight of the 27 patients are alive and diseasefree after the second HSCT. One patient is alive and disease-free after two allogeneic transplants (day +1538), eight patients, who relapsed after an autologous transplant followed by an allogeneic transplant (days +248 to +1140), acute myeloid leukaemia (n = 6) and chronic myeloid leukemia (n = 2) are alive and diseasefree. The overall disease-free survival is 30% (8/27). The overall disease-free survival of autologous transplant patients subsequently undergoing an allogeneic transplant is 43% (P = 0.049). It is suggested that a second HSCT is possible for patients with leukemia relapse following the first autologous transplant. A second transplant might also be offered to patients relapsing after the first allogeneic HSCT. Keywords: second allogeneic bone marrow transplant; conditioning regimen; relapse rate; acute leukemia; diseasefree survivalThe relapse rate in patients transplanted for acute or chronic leukemia still ranges from 20-60%, accounting for one important cause of treatment failure. 1,2 Relapse rate correlates with diagnosis and stage of disease, 3,4 since patients transplanted either in relapse or after chemotherapy induction failure demonstrated a significantly higher risk for relapse compared to patients transplanted in complete remission. 5 The management of patients relapsing after HSCT is still controversial. 6,7 The therapeutic modalities for the treatment of leukemia relapse following allogeneic transplantation have been reviewed recently. [8][9][10] Options such as immunotherapy, donor lymphocyte infusion (DLI) or a second allograft after myeloablative conditioning have been explored. 10 Despite the high treatment-related mortality with a second HSC ...
Summary:We compared the outcomes in patients receiving unrelated peripheral blood stem cell transplants (PBSCT) with those receiving bone marrow transplants (BMT) in a matched pair analysis. Seventy-four patients with hematological malignancies with HLA-matched (77%) and mismatched (23%) donors were analyzed in this study. Thirty-four patients (45%) were considered as high risk patients. Sixty-eight patients received standard conditioning regimens with Bu/Cy or TBI/Cy. Six patients received an intensified conditioning regimen with the addition of etoposide, thiotepa or melphalan. GVHD prophylaxis consisted of prednisolone, cyclosporine and methotrexate. Groups were matched for patient, donor, transplant characteristics and HLA compatibility. Peripheral blood stem cell collection led to the collection of a higher number of CD34 + and CD3 + cells in comparison to bone marrow collection. Leukocyte engraftment in the PBSCT group occurred in 14 days (median; range 6-26 days) and in the BMT group in 19 days (range 9-29 days; P Ͻ 0.02). The time of platelet engraftment did not differ significantly. The incidence of grades II-lV acute GVHD in the group of HLA-identical patients was 35% in the PBSCT group and 25% in the BMT group (P Ͻ 0.33, log-rank). However, there was a significant difference (P Ͻ 0.05, logrank) in incidence and time to onset of acute GVHD II-IV comparing all patients, including the 17 mismatched transplants. Disease-free survival was 51% (19 patients) with a median of 352 days and 59% (21 patients) with a median of 760 days for PBSC and BMT transplants, respectively. In conclusion, our results indicate that allogeneic PBSCT led to significantly faster leukocyte engraftment but is associated with a higher incidence and more rapid onset of severe acute GVHD comparing all patients, including the 17 mismatched transplants. However, the incidence of severe acute GVHD in HLAidentical patients was not different between the PBSCT and BMT groups. Bone Marrow Transplantation (2001) 27, 27-33.
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