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.
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/m [MTX15] and 10 mg/m [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. This trial is registered at CTRI/2010/091/001480.
Autologous transplantation is the standard of care for transplant-eligible patients with multiple myeloma. Toward making this treatment accessible in developing countries, there are significant challenges like resource constraints and access to cryopreservation facilities. We performed a retrospective analysis of patients with multiple myeloma who underwent autologous transplantation using granulocyte colony-stimulating factor (G-CSF)-mobilized non-cryopreserved grafts at our institution from January 1995 to December 2014. Peripheral blood stem cells (PBSCs) were harvested over 1 to 2 days after G-CSF mobilization. After apheresis, PBSCs were stored at 4°C in a blood bank refrigerator for up to 72 hours. During the study period, 224 patients with multiple myeloma underwent autologous transplantation using G-CSF-mobilized non-cryopreserved grafts. The number of days of stem cell harvest was 1 in 91 patients (40.6%) and 2 in 133 patients (59.4%). The median CD34 cell dose was 4.87 × 10/kg (range, 1.15 to 23.7). All patients except 1 engrafted. The median time to neutrophil engraftment was 12 days (range, 9 to 22). The median time to platelet engraftment was 17 days (range, 10 to 44). In a resource-limited setting, the use of G-CSF-mobilized non-cryopreserved grafts results in adequate engraftment for most patients with multiple myeloma undergoing autologous stem cell transplantation.
There is paucity of data from developing countries on the clinical outcomes in myeloma post-autologous transplantation. In this retrospective study, we used hospital records to retrieve data of patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) from January 1995 to December 2014 at our centre. During the study period, 245 patients underwent ASCT for myeloma. Of these, 19%, 37% and 37% were in complete response, very good partial response and partial response respectively at the time of ASCT. Only in 14 (5.7%) patients, the stem cells were cryopreserved. The transplant related mortality was 2.86%. The median follow up was 40.7 months (range 0-237.4 months). The 5-year overall survival (OS) and progression-free survival (PFS) for the entire cohort was 61.6% ± 3.8% and 37.2% ± 3.9% respectively. Independent predictors of OS included mononuclear cell dose infused, pre-and post-transplant response; and the use of maintenance therapy. Independent predictors of PFS included age at diagnosis, pre-and posttransplant response; and the use of maintenance therapy. In a resource limited setting, ASCT for myeloma is associated with low transplant related mortality. Pre-and post-transplant response and maintenance therapy are predictors of survival.
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.
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