11 research outputs found
T-Cell Depleted Allografts From Unrelated Donors Confer A Low Risk Of Relapse On Patients With Hematologic Malignancies
Increased growth and collagen synthesis of bone marrow fibroblasts from patients with chronic myelocytic leukaemia
Myelofibrosis in chronic granulocytic leukaemia: clinicopathologic correlations and prognostic significance
Fractionated Infusion of Hematopoietic Progenitor Cells Does Not Improve Neutrophil Recovery or Survival in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies
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Induction of Remission Prior to Transplantation Improves the Disease-Free Survival (DFS) of Patients with Advanced Myelodysplastic Syndromes (MDS) Treated with Myeloablative T - Cell Depleted (TCD) Stem Cell Transplants (SCT) from Histocompatible Unrelated Donors
Abstract
Disease relapse and transplant-related mortality (TRM) have been the two major problems limiting the success of unrelated donor SCT in patients with advanced MDS (RAEB 1 and 2 and AML evolved from MDS). Induction of remission is an approach that has been used to reduce the incidence of relapse, but its use remains controversial. T cell depletion of allografts has been used to reduce the incidence of graft-versus-host disease and TRM. From 1989 to 2004, 28 patients with advanced MDS underwent bone marrow or peripheral blood SCT from molecularly matched (HLA A, B, C, DRB1 and DQB1 - 18 patients) or partially mismatched (maximum 2 antigen mismatch allowed - 10 patients) volunteer donors following conditioning with myeloablative conditioning with total body irradiation (1375 cGy), thiotepa (10 mg/kg) and cyclophosphamide (120 mg/kg) or fludarabine 125 mg/kg) - 17 patients, or busulfan (8 mg/kg), melphalan (140 mg/kg) and fludarabine (125 mg/kg) - 11 patients. Twenty six patients received chemotherapy (2 low dose and 24 induction doses) prior to conditioning, and 2 patients did not receive any chemotherapy. Prior to transplant, 18 of the 28 treated patients were in hematologic remission (CR), 2 in a second refractory cytopenia phase (RCy2) (20 responders), and 6 had failed to achieve remission or their MDS had relapsed. The marrow grafts were depleted of T cells using the soybean agglutinin method and then sheep red blood cell rosetting (15 patients) and the G-CSF-mobilized peripheral blood stem cell (PBSC) grafts with CD34 selection and E-rosetting (13 patients). Rejection prophylaxis with anti-thymocyte globulin was used in all 28 patients. Posttransplant pharmacologic prophylaxis for GvHD was given only to 1 patient. The median age was 49.9 years (range 4–59.6), 14 patients were ≥ age 50. Two patients died before engraftment and 26 engrafted; 2 of them had late graft failure. Eight patients developed acute GvHD (grades 2 to 4) and 2 chronic GvHD (1 limited). The DFS in these three group of patients was significantly different (p= 0.0004). The DFS at 5 years was 55% for the patients in CR and RCy2, 33% for the failures, and no patients were alive in the untreated group. DFS was worse in patients with high risk IPSS. DFS was slightly better in patients cytoreduced with the busulfan-containing regimen, 72% versus 29% (p = 018). DFS was not statistically different in the recipients of matched (39%) or mismatched (60%) transplants. The cumulative incidence (CI) of relapse at 2-years posttransplant for the responders was 5.5%, for the failures 25%, and for the untreated group 50%. The CI of non-relapse mortality or TRM at 2-years posttransplant for the responders was 33.33%, for the failures was 62.5%, and for the untreated was 50%. All survivors have achieved ≥KPS 90%. These observations confirm the value of induction of remission prior to conditioning as a means to reduce the incidence of disease relapse in the posttransplant period and show that T cell depletion decreases the TRM in these patients receiving unrelated stem cell transplants
T-Cell Depleted Allografts From Unrelated Donors Confer A Low Risk Of Relapse On Patients With Hematologic Malignancies
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Induction of Remission Prior to Transplantation Improves the Disease-Free Survival (DFS) of Patients with Advanced Myelodysplastic Syndromes (MDS) Treated with Myeloablative T-Cell Depleted (TCD) Stem Cell Transplants (SCT) from HLA Identical Siblings
Abstract
Posttransplant relapse is a major limitation to the success of allogeneic SCT in patients with advanced MDS (refractory anemia with excess blasts (RAEB I and II), refractory anemia in transformation (RAEB-t), and acute myeloid leukemia transformed from MDS). The use of induction chemotherapy prior to transplant to induce remission and thereby to reduce posttransplant relapse in these patients remains controversial. From 1985 to 2004, 47 patients with advanced MDS underwent bone marrow or peripheral blood SCT from HLA identical siblings after myeloablative conditioning with total body irradiation (TBI) and cyclophosphamide alone or in some combined with thiotepa, carboplatinum, diaziquone, or etoposide, or TBI combined with thiotepa and fludarabine. Thirty-six patients received low dose (3 patients) or full induction (33 patients) chemotherapy before conditioning, and 11 patients did not receive any chemotherapy. Prior to transplant, 22 of the 36 treated patients were in hematologic remission (CR) and 4 achieved a second refractory cytopenia phase (RCy2) for a total of 26 responders, and 10 had failed to respond to chemotherapy. Marrow grafts were depleted of T cells using soybean lectin agglutination and then sheep RBC-rosetting (n=32 patients). G-CSF-mobilized peripheral blood stem cell (PBSC) grafts underwent positive CD34 selection and T-cell depletion by sheep RBC-rosetting (n=10 patients). Five patients received a marrow graft followed by a PBSC allograft from the same donor because of low marrow cell dose. Rejection prophylaxis with anti-thymocyte globulin was used in 33 patients. No posttransplant pharmacologic prophylaxis for GvHD was given. The median age was 48 years (range 13–61). Forty-three of the 47 patients in this series engrafted, and 2 had primary graft failure. Two patients died before engraftment. Only 3 patients developed acute GvHD (grades 1 and 3) and 1 chronic GvHD. At 5 years posttransplant, the DFS was 44% for the patients in CR and RCy2 at time of transplant, but no patients in the untreated group or in the chemotherapy failure group survived (p=0.0004). The cumulative incidence (CI) of relapse at 2-years posttransplant for the responders was 27.0%, for the failures 50%, and for the untreated group 45%. The CI for non-relapse mortality at 2-years posttransplant was 19% for the responders, 40% for the failures, and 36% for the untreated patients. All survivors have achieved ≥KPS 90%. These results indicate that patients with advanced MDS who achieve remission or a second refractory anemia phase with chemotherapy before TCD allogeneic SCT can achieve successful long-term remisions. In contrast, the high incidence of posttransplant relapse mitigates against the use of TCD SCT in patients with advanced MDS with active disease (≥5% blasts) prior to transplant. Prospective multicenter randomized studies are needed to validate the value of pre-transplant chemotherapy in patients with advanced MDS undergoing allogeneic SCT