Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Jul 2010
Unrelated transplantation for poor-prognosis adult acute lymphoblastic leukemia: long-term outcome analysis and study of the impact of hematopoietic graft source.
Adults with high-risk acute lymphoblastic leukemia (HR-ALL) have a poor outcome with standard chemotherapy and usually undergo unrelated stem cell transplantation (SCT) if a matched sibling donor is not available. We analyzed the outcome of adult patients with unrelated SCT for HR-ALL and studied the possible effect of the hematopoietic stem cell source of the transplant. A total of 149 adult patients (median age, 29 years, range, 15-59 years) with HR-ALL underwent unrelated SCT in 13 Spanish institutions between 2000 and 2007. ⋯ All unrelated transplantation modalities were associated with high treatment-related mortality for adult HR-ALL patients without a sibling donor. UCB-SCT and UD-SCT were found to be equivalent options. Disease status at transplantation and chronic GVHD were the main factors influencing relapse in both transplantation modalities.
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Biol. Blood Marrow Transplant. · Jul 2010
Randomized Controlled TrialA randomized phase II trial comparing tacrolimus and mycophenolate mofetil to tacrolimus and methotrexate for acute graft-versus-host disease prophylaxis.
Tacrolimus (Tac) plus methotrexate (MTX) is a standard regimen for graft-versus-host disease (GVHD) prophylaxis. Mycophenolate mofetil (MMF) is sometimes used instead of MTX to minimize toxicity, despite the lack of controlled studies demonstrating efficacy. We conducted a single-center, randomized phase II trial comparing Tac + MMF to Tac + MTX. ⋯ Moderate or severe chronic GVHD was similar (P = .71). There were no significant differences between the arms in relapse, nonrelapse mortality, or overall and relapse-free survivals. MMF was associated with less early toxicity than MTX but was not as effective in preventing severe aGVHD, especially in unrelated donor transplants.
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Biol. Blood Marrow Transplant. · Jul 2010
Protective immunity transferred by infusion of cytomegalovirus-specific CD8(+) T cells within donor grafts: its associations with cytomegalovirus reactivation following unmanipulated allogeneic hematopoietic stem cell transplantation.
Human cytomegalovirus (CMV)-specific cytotoxic T lymphocyte (CTL) immune response must be reconstituted for long-term protection against CMV relapse and disease in hematopoietic stem cell transplantation (HSCT) recipients. We phenotypically quantitated absolute numbers of CMV-pp65 peptide-specific CTLs (CTL(CMV)) in 50 related donor unmanipulated allografts infused into HLA-matched or -mismatched recipients and examined the incidence of CMV reactivation. High CTL(CMV) with terminally differentiated effector CD45RO(-)CD62L(-) cell (T(EMRA)) phenotype in the allografts were associated with reduced risk of CMV reactivation, in the presence of sufficient CD45RO(+)CD62L(-) cell (T(EM)) infusion (>/=0.208 x 10(6)/kg). ⋯ The frequencies of CTL(CMV) T(Naive) (CD45RO(-)CD62L(+)), T(CM), and T(EM) at day 90 posttransplantation and of CTL(CMV) T(EMRA) at day 60 posttransplantation were greater in recipients with higher infusions of CTL(CMV) T(EMRA), suggesting protective immunity transferred by infusion of CTL(CMV) within allografts. Moreover, the majority of the CTL(CMV) identified in the recipients early after HSCT was of donor origin. Our findings support that measuring levels of CTL(CMV) and its subsets in the donor grafts and manipulating these cells early after transplantation may help control CMV reactivation, which is closely correlated with immune reconstitution and differentiation of CTL(CMV) subsets.
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Biol. Blood Marrow Transplant. · Jun 2010
Clinical TrialCotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning.
Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD) after myeloablative allogeneic HCT. This prompted us to investigate in a pilot study whether MSC infusion before HCT could allow nonmyeloablative (NMA) HCT (a transplant strategy based nearly exclusively on graft-versus-tumor effects for tumor eradication) from HLA-mismatched donors to be performed safely. Twenty patients with hematologic malignancies were given MSCs from third party unrelated donors 30-120 minutes before peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors, after conditioning with 2 Gy total body irradiation (TBI) and fludarabine. ⋯ One-year NRM (10%), relapse (30%), overall survival (OS) (80%) and progression-free survival (PFS) (60%), and 1-year incidence of death from GVHD or infection with GVHD (10%) were encouraging. These figures compare favorably with those observed in a historic group of 16 patients given HLA-mismatched PBSCs (but no MSCs) after NMA conditioning, which had a 1-year incidence of NRM of 37% (P = .02), a 1-year incidence of relapse of 25% (NS), a 1-year OS and PFS of 44% (P = .02), and 38% (P = .1), respectively, and a 1-year rate of death from GVHD or infection with GVHD of 31% (P = .04). In conclusion, our data suggest that HLA-mismatched NMA HCT with MSC coinfusion appeared to be safe.
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Biol. Blood Marrow Transplant. · Jun 2010
Clinical TrialHepatitis B virus reactivation and efficacy of prophylaxis with lamivudine in patients undergoing allogeneic stem cell transplantation.
Patients previously infected with hepatitis B virus (HBV) undergoing an allograft and recipients from HBV carrier donors are at risk of posttransplant viral reactivation. The role of prophylaxis with lamivudine remains unclear. One hundred seventeen patients, with a median age of 52 years (20-67 years), with various hematologic malignancies transplanted between 1999 and 2007 entered the study. ⋯ Hepatitis developed in 3 anti-HBc positive untreated patients conditioned with a reduced-intensity regimen. Hepatitis B was not observed in recipients at low risk, transplanted from HBsAg negative/anti-HBc positive or negative donors. Lamivudine was effective in controlling reactivation in: HBsAg positive recipients, in patients transplanted from HBsAg positive donors and in HBsAg negative/antiHBc positive recipients, who showed a significant risk of reactivation if not given prophylaxis (NCT 00876148).