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Allogeneic hemopoietic stem cell transplantation (allo- HSCT) poses a significant challenge to renal function due to multiple drug- and complication-related renal toxicity. In this single-center series of 216 adult Asian patients with a long and complete follow-up, 41 developed chronic kidney disease ( CKD) giving a cumulative incidence of 19.0% at 25 years (median follow-up duration 7.84 years, range 2.0-27.7 years), but only two of the 41 patients reached stage 4 CKD and another two required dialysis. In contrast, acute kidney injury occurred in most patients, where glomerular filtration rate ( GFR) suffered a mean fall of 50 mL/min/1.73 m2 at 6 months post-transplant compared with baseline. Suppression of renal function may last beyond 6 months but is potentially reversible, although not to baseline level in most patients. Analysis of a comprehensive range of 18 risk factors showed that older age, lower GFR at transplant, unrelated donor, diagnosis of AML, presence of diabetes mellitus at transplant, and duration of foscarnet use were significantly associated with CKD development, with the first three remaining as independent risks for CKD in multivariate analysis. Long-term survival is not affected by renal function, being 78.6% as compared to 85.5% for patients with low vs normal GFR at 2 years, respectively. [ABSTRACT FROM AUTHOR]

To better understand predictive factors and improve the clinical outcome of allogeneic transplant for patients with Philadelphia positive acute lymphoblastic leukemia, we analyzed 67 Southeast Asian patients transplanted in our institutions. Multivariate analysis showed that disease status before transplant, year of transplant and, interestingly, French-American-British (FAB) subtype had a significant impact on overall survival (OS) and non-relapse mortality. Patients who were minimal residual disease (MRD) negative at transplant had a 3-year OS of 73% compared to those who were MRD positive (45%) and refractory (0%). The 3-year cumulative incidence of relapse was 18% and 36% for the MRD negative and positive groups, respectively. FAB L1 subtype had a significantly superior 3-year OS of 63% vs. 29% for L2 subtype. Pre-transplant use of a tyrosine kinase inhibitor significantly improved outcomes in univariate but not multivariate analysis, as it served to induce more patients into MRD negativity, which was the factor that directly improved transplant outcome. [ABSTRACT FROM AUTHOR]

Abstract: Haploidentical hematopoietic stem cell transplantation (HSCT) provides an opportunity for patients to benefit from HCT when a human leukocyte antigen (HLA) genotypically matched sibling is not available. Initial results with the use of mismatched allograft has been disappointing due to the high incidence of graft-versus-host disease (GVHD) and infectious complications resulting in an unacceptable treatment-related morbidity and mortality. Recent advances with effective T-cell depletion, the use of ‘megadose’ of stem cells and reduced intensity conditioning has significantly decreased the early transplant related mortality and GvHD, while enabling robust and prompt engraftment, and hence enhancing the therapeutic benefits of haploidentical transplantation. However, the cardinal problems related to delayed immune reconstitution causing posttransplant infectious complications and relapse remain, limiting the efficacy of haploidentical transplant. Preliminary data have demonstrated the great potential in the use of adoptive cellular immunity and selective allodepletion in rapidly reconstituting immunity without GvHD. The encouraging reports from haploidentical transplant using noninherited maternal antigen (NIMA)-mismatched donors or natural killer alloreactive donors may greatly increase the donor availability and open a way to more appropriate donor selection in HLA-haploidentical HSCT. Future challenges remain in determining the safest approach for haploidentical transplant to be performed with minimal risk of GvHD, while preserving effective graft-versus-leukemia activity and promoting prompt immune reconstitution. [Copyright &y& Elsevier]

Abstract: Haploidentical hematopoietic stem cell transplantation (HSCT) provides an opportunity for nearly all patients to benefit from HSCT when a human leukocyte antigen (HLA) genotypically matched sibling is not available. Initial results with the use of mismatched allografts led to limited enthusiasm because of graft-versus-host disease (GVHD) and infectious complications, resulting in an unacceptable treatment-related morbidity and mortality. Recent advances with effective T cell depletion, the use of a “megadose” of stem cells, earlier detection of severe infections, combined with better antimicrobial therapy and reduced-intensity conditioning (RIC) has significantly decreased the early transplant-related mortality and GVHD, whereas enabling prompt engraftment, hence advancing the therapeutic benefit of haploidentical transplantation. However, the cardinal problems related to delayed immune reconstitution allowing posttransplant infectious complications and relapse remain, limiting the efficacy of haploidentical HSCT. Preliminary data has demonstrated the potential for use of adoptive cellular immunity and selective allodepletion in rapidly reconstituting immunity without GVHD. The encouraging reports from haploidentical transplant using noninherited maternal antigen (NIMA)-mismatched or natural killer (NK) alloreactive donors may greatly increase the donor availability and open the way to more appropriate donor selection in HLA-haploidentical HSCT. Future challenges remain in determining the safest approach for haploidentical transplant to be performed with minimal risk of GVHD, whereas preserving effective graft-versus-leukemia activity and promoting prompt immune reconstitution. [Copyright &y& Elsevier]

Abstract: The development of nonmyeloablative (NM) hematopoietic cell transplantation (HCT) has extended the potential curative treatment option of allografting to patients in whom it was previously contraindicated because of advanced age or comorbidity. Acute and chronic graft versus host disease (GVHD) and its consequent nonrelapse mortality (NRM), remains the major limitation of NM HCT. In this report, we analyzed the outcome of 67 patients (median age, 45 years) with hematologic diseases receiving NM conditioning with fludarabine 90 mg/m2 and total body irradiation (TBI) 200-cGy, followed by filgrastim-mobilized peripheral blood stem cell transplant from HLA identical (n = 61), 5/6 antigen-matched related (n = 1), 6/6 antigen-matched unrelated (n = 3), and 5/6 antigen-matched unrelated (n = 2) donors. The first cohort of 21 patients were given cyclosporine (CSP) and mycophenolate mofetil (MMF) as postgrafting immunosuppression, whereas the subsequent cohort was given additional methotrexate (MTX) and extended duration of CSP/MMF prophylaxis in an attempt to reduce graft-versus-host disease (GVHD). Sixty-four (95%) patients engrafted and 3 (5%) had secondary graft failure. Myelosuppression was moderate with neutrophil counts not declining below 500/μL in approximately 25% of patients, and with more than half of the patients not requiring any blood or platelet transfusion. The 2-year cumulative interval (CI) of grade II-IV, grade III-IV acute GVHD and chronic GVHD were 49%, 30%, and 34%, respectively. The 2-year probability of NRM, overall (OS), and progression-free (PFS) survival were 27%, 43%, and 28%, respectively. GVHD-related death accounted for 85% of NRM. Compared with patients receiving CSP/MMF, patients receiving extended duration of CSP/MMF with additional MTX in postgrafting immunosuppression had a significantly lower risk of grade III-IV acute GVHD (CI 20% versus 52%; P = .009) and NRM (CI at 2 years: 11% versus 62%; P < .001), without any significant adverse impact on the risk of relapse (CI at 2 years: 59% versus 33%; P = .174) Subgroup analysis of a cohort of patients given MTX/CSP/MMF showed that patients with “standard risk” diseases (n = 21) had a 3-year OS and PFS of 85% and 65%, respectively. This compares favorably to the 41% (P = .02) and 23% (P = .03) OS and PFS, respectively, in patients with “high-risk” diseases (n = 25). In conclusion, the addition of MTX onto the current postgrafting immunosuppression regimen with extended CSP/MMF prophylaxis duration provides more effective protection against severe GVHD, and is associated with more favorable outcome in patients receiving NM fludarabine/TBI conditioning than in patients receiving fludarabine/TBI conditioning with CSP and MMF without MTX. [Copyright &y& Elsevier]

Unrelated umbilical cord blood (UCB) transplantation has recently been explored in an increasing number of adult patients. The relative ease of procurement and the lower-than-anticipated risk of severe acute graft-versus-host disease has made UCB transplantation an appealing alternative to bone marrow-derived hematopoietic stem cells. The use of reduced-intensity or nonmyeloablative preparative regimens to allow engraftment of UCB broadens the scope of patients who may benefit from allogeneic immunotherapy, including elderly and medically infirm patients with no matched sibling donor. This review summarizes the available data on the use of UCB as an alternative source of hematopoietic stem cell transplantation in adult patients. [Copyright &y& Elsevier]

The article discusses the computed tomography findings in a patient with severe graft-versus-host disease (GvHD) of the gut. A 47-year-old women with chronic myeloid leukemia in accelerated phase underwent an allogeneic peripheral blood stem cell transplant from her human leucocyte antigenidentical sibling after non-myeloablative conditioning. The transplant was uneventful and she achieved a complete cytogenetic remission with full donor chimaerism.