Iracema Esteves

Haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with X-linked adrenoleukodystrophy: a suitable choice in an urgent situation

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment that enhances survival and stabilizes neurologic symptoms in X-linked adrenoleukodystrophy (X-ALD) with cerebral involvement, a severe demyelinating disease of childhood. Patients with X-ALD who lack a well-matched HLA donor need a rapid alternative. Haploidentical HSCT using post transplant cyclophosphamide (PT/Cy) has been performed in patients with malignant and nonmalignant diseases showing similar outcomes compared to other alternative sources. We describe the outcomes of transplants performed for nine X-ALD patients using haploidentical donors and PT/Cy. Patients received conditioning regimen with fludarabine 150 mg/m2, cyclophosphamide 29 mg/kg and 2 Gy total body irradiation (TBI) with or without antithymocyte globulin. Graft-vs.-host disease prophylaxis consisted of cyclophosphamide 50 mg/kg/day on days +3 and +4, tacrolimus or cyclosporine A and mycophenolate mofetil. One patient had a primary graft failure and was not eligible for a second transplant. Three patients had secondary graft failure and were successfully rescued with second haploidentical transplants. Trying to improve engraftment, conditioning regimen was changed, substituting 2 Gy TBI for 4 Gy total lymphoid irradiation. Eight patients are alive and engrafted (17–37 months after transplant). Haploidentical HSCT with PT/Cy is a feasible alternative for X-ALD patients lacking a suitable matched donor. Graft failure has to be addressed in further studies.

Human Leukocyte Antigen–Haploidentical Transplantation for Relapsed/Refractory Hodgkin Lymphoma: A Multicenter Analysis

Reduced-intensity-conditioned allogeneic stem cell transplantation (SCT) remains a potentially curative approach for patients with relapsed/refractory Hodgkin lymphoma (HL) after an autologous stem cell transplantation. In the absence of an HLA-identical donor, haploidentical SCT (haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy) has been evaluated with favorable preliminary results. We evaluated 24 patients who underwent haplo-SCT for relapsed/refractory HL. The conditioning regimen consisted of cyclophosphamide, fludarabine, and total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of a calcineurin inhibitor, mycophenolate mofetil, and PT-Cy (50 mg/kg/day for 2 days) for all patients. After a median follow-up of 2 years, the cumulative incidence (CI) of nonrelapse mortality was 26% and the CI of grades II to IV acute GVHD and chronic GVHD were 17% and 24%, respectively. Estimation of progression-free and overall survival at 2 years were 54% and 66%%, respectively. Haplo-SCT is a valuable option for relapsed/refractory HL patients after a failed autologous SCT, with favorable survival and relatively low risk of GVHD.

Endoscopy Biopsy in Different Sites for the Diagnosis of Lower and Upper Gastrointestinal Graft-Versus-Host Disease

Cell dose is a major criterion for cord blood unit (CBU) selection for allogeneic stem cell transplantation (allo-SCT). The aim of this study was the characterization of CBU cellular composition after thaw, and comparisonwith corresponding values at cryopreservation as reported by cord blood (CB) banks. The study included 87 CBUs, that were thawed for infusion in the context of single (n1⁄43) or dual-unit (n1⁄442) allo-SCT in adults with hematologic malignancies, from 8/2006 to 6/2013. Upon thawing, the cryoprotective solution (DMSO 10%) was either removed by centrifugation/washing (38 CBUs) or diluted in a less hypertonic solution of Dextran 40/Human Albumin 2.5% (49 CBUs). Total nucleated cells (TNC) were measured with a hematology analyzer, while enumeration of CD34+ stem cells was performed by singleplatform flow cytometry, according to ISHAGE guidelines. In 49 units, TNC and CD34+ cell viability was evaluated by addition of 7-AAD dye and sequential Boolean gating strategy. TNC counts after thawing were lower compared to their values at freezing (Wilcoxon test, p <10-4), and the difference was more pronounced in the units that were washed prior to infusion (Tables 1 and 2). Total cell viability was low (mean value, 42.6%), but this was mainly due to neutrophils. Regarding CD34+ cells, there was a significant difference between absolute counts at cryopreservation and at thaw (p<10-4). Despite reduction postthaw, the counts of both TNC and CD34+ cells did correlate with the corresponding values at cryopreservation by Spearman’s analysis. Of note, washing seemed slightly advantageous in terms of CD34+ recovery (Tables 1 and 2). CD34+ cells retained high viability after thaw, with 90% of CBUs (44 out of 49 tested) demonstrating CD34+ viability 80%. Viability of <50% was noticed in only one CBU that failed to engraft. In conclusion, CB cellular content and especially the CD34+ cell count is frequently shown to be inferior at thaw compared to cryopreservation. This probably reflects both the lack of standardization of CD34+ cell measurement and the effect of thawing procedure. Therefore, CD34+ cell viability may be a more meaningful marker for determining CBU quality. GVH/GVL

Use of gemtuzumab ozogamycin combined with conventional chemotherapy in patients with acute myeloid leukemia

OBJECTIVE To analyze the outcome of patients treated with gemtuzumab ozogamycin combined with conventional therapy treated at Hospital Israelita Albert Einstein. METHODS 14 patients who had high risk features (secondary leukemia, unfavorable cytogenetics, and refractory disease) were treated with gemtuzumab ozogamycin combined with conventional therapy and their outcome was analysed by reviewing their medical records. RESULTS Overall response rate was 58%, with 43% achieving complete response, with a median follow-up of 11 months, event-free survival was 3 months. Eleven patients died, 6 of them due to refractory acute myeloid leukemia. Only four patients presented with grade 3 to 4 toxicities and only one patient had sinusoidal obstruction syndrome after bone marrow transplant. CONCLUSION gemtuzumab ozogamycin combined with chemotherapy is a feasible treatment regimen in acute myeloid leukemia patients. However, further studies are necessary to clarify which subgroup of patients may beneft from this treatment.