Post-transplant cyclophosphamide as sole graft-versus-host disease prophylaxis is feasible in patients undergoing peripheral blood stem cell transplantation for severe aplastic anemia using matched sibling donors

High-dose cyclophosphamide (PTCY) after allogeneic hematopoietic cell transplantation (HSCT) has been shown to be effective in preventing graft-versus-host disease (GVHD) after HLA-matched bone marrow transplantation. We performed a phase II study of PTCY given at 50 mg/kg i.v. on days 3 and 4 as the sole GVHD prophylaxis after HSCT for severe aplastic anemia (SAA) in patients receiving granulocyte colony-stimulating factor–mobilized peripheral blood stem cell (PBSC) grafts from HLA-matched related donors after conditioning with fludarabine, CY, and single-dose total body irradiation. Thirty patients with a median age of 29 years (range, 16 to 49) were enrolled in this study. Engraftment was seen in 27 patients (90%) at a median of 16 days (range, 12 to 21) post-HSCT. None of the patients developed veno-occlusive disease of the liver or hemorrhagic cystitis. Grades II to IV acute GVHD was seen in 22% of patients with grades III to IV GVHD in 11.1%. The 2-year cumulative incidence of chronic GVHD was 22.7%. Fourteen patients (46.6%) did not require any further immunosuppression after receiving PTCY. Comparing with 2 historical cohorts of 30 patients each who received cyclosporine and methotrexate (MTX; at 15 mg/m² [MTX15] and 10 mg/m² [MTX10]), the incidence of grades II to IV acute GVHD was lower, albeit not significantly, with the use of PTCY (PTCY, 22.2%, vs MTX15, 37.1%, vs MTX10, 53.8%; P = .056), whereas rates of chronic GVHD were significantly reduced (PTCY, 22.7%, vs MTX15, 63.6%, vs MTX10, 76.2%; P = .013). Viral infections including cytomegalovirus were significantly higher with the use of PTCY (60%) compared with cyclosporine and MTX (MTX15, 23.3%, vs MTX10, 33.3%; P = .008). Overall survival was similar between the 3 groups. We conclude that PTCY as the sole GVHD prophylaxis is associated with low rates of acute and chronic GVHD in patients undergoing PBSC transplant for SAA using HLA-matched donors

Second hematopoietic stem cell transplant for thalassemia major: improved clinical outcomes with a treosulfan-based conditioning regimen

Graft rejection (GR) after allogeneic stem cell transplantation (allo-SCT) occurs in 10% to 20% of patients with β-thalassemia major (TM). There are limited data on the clinical profile and long-term outcome of patients who have had a GR. We undertook a retrospective analysis of patients who had a graft failure after allo-SCT for TM at our center. From October 1991 to June 2016, 55 of 506 patients (11%) transplanted for TM had a graft failure. An additional 7 patients with graft failure after allo-SCT done at other centers were referred to us for a second transplant. The median age was 8 years (range, 1 to 19), and there were 38 males (61.2%). Thirty-two patients (52.4%) were primary graft failures (15 with aplasia and 17 with autologous recovery) and 30 (47.6%) were secondary graft failures (5 with aplasia and 25 with autologous recovery). On conventional risk stratification 40 patients (64.5%) were class III. Seventeen patients (53.12%) with primary graft failure and 16 (53.3%) with secondary graft failure did not receive a second transplant. Twenty-nine patients (46%) with GR underwent a second allo-SCT. With the exception of 1 patient (first allo-SCT with an unrelated cord blood product), the donor for the second transplant was the same as the first transplant. Conditioning regimen for the second SCT was busulfan-based myeloablative (MAC) in 7 patients (24%), treosulfan-based MAC in 12 patients (41.3%), and the remaining received non-MAC regimens in view of pancytopenia and perceived inability to tolerate MAC. None of the patients conditioned with a treosulfan-based regimen had a GR, although 1 patient died with complications secondary to chronic graft-versus-host disease. Of the remaining 17 patients, 10 died after the second GR and 3 of regimen-related toxicity. Four are alive, of which 1 has recurrent TM and the rest are well and transfusion independent at 55, 80, and 204 months, respectively, from second transplant (all busulfan-based MAC). On a univariate analysis a nontreosulfan-based conditioning regimen and time from GR to second transplant of <1 year was significantly associated with an adverse impact. However, on a multivariate analysis only a nontreosulfan-based regimen was associated with a significant adverse impact on event-free survival (HR, 11.5; 95% CI, 1.13 to 116.4; P = .039). In conclusion, there has been a significant improvement in clinical outcomes in our experience with the use of a treosulfan-based reduced-toxicity MAC regimen for second allo-SCT for TM. It would be reasonable, where feasible, to defer the second transplant by a year after the first GR

Adult Acute Lymphoblastic Leukemia: Limitations of Intensification of Therapy in a Developing Country

Purpose: Limited data exist on intensifying chemotherapy regimens in the treatment of adult acute lymphoblastic leukemia (ALL) outside the setting of a clinical trial. Materials and Methods: Retrospectively, data from 507 consecutive adults (age ≥ 15 years) with a diagnosis of ALL treated at our center were analyzed. Standard-risk (SR) patients were offered treatment with a modified German Multicenter ALL (GMALL) regimen, whereas high-risk (HR) patients were offered intensification of therapy with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD). Because of resource constraints, a proportion of HR patients opted to receive the same treatment regimen as used for SR patients. Results: There were 344 SR patients (67.8%) and 163 HR patients (32.2%) at diagnosis. Among the HR patients, 53 (32.5%) opted to receive intensification with the HCVAD regimen. The SR cohort showed a superior 5-year event-free survival rate compared with the HR cohort (47.3% v 23.6%, respectively; P < .001). Within the HR subgroup, there was no statistically significant difference in overall survival or event-free survival between patients who received the modified GMALL regimen (n = 59) and patients who received HCVAD (n = 53). Conclusion: Intensified therapy in the HR subset was associated with a significant increase in early treatment-related mortality and cost of treatment. A modified GMALL regimen was found to be cost-effective with clinical outcomes comparable to those achieved with more intensive regimens