Comparison between reduced intensity and conventional myeloablative allogeneic stem-cell transplantation in patients with hematologic malignancies aged between 50 and 59 years

Abstract

Summary:To evaluate the efficacy of reduced-intensity stem-cell transplantation (RIST), we retrospectively compared outcomes of 207 consecutive Japanese patients aged between 50 and 59 years with hematologic malignancies who received RIST (n ¼ 70) and conventional stem-cell transplantation (CST) (n ¼ 137). CST recipients received total body irradiation (TBI)-based or busulfan/cyclophosphamide-based regimens. RIST regimens were purine analog-based (n ¼ 67), 2 Gy TBI-based (n ¼ 2), and others (n ¼ 1). Most CST recipients (129/137) received calcineurin inhibitors and methotrexate as graft-versus-host (GVHD) prophylaxis, while 32 RIST recipients received cyclosporin. In all, 23 CST and five RIST recipients died without disease progression within 100 days of transplant. Grade II to IV acute GVHD occurred in 56 CST and 38 RIST recipients. There was no significant difference in overall survival (OS) and progression-free survival between CST and RIST. On multivariate analysis on OS, five variables were significant: preparative regimens (CST vs RIST) (hazard ratio ¼ 1.92, 95% confidence interval, 1.25-2.97; P ¼ 0.003), performance status (2-4 vs 0-1) (2.50, 1.51-4.16; Po0.001), risk of underlying diseases (1.85, 1.21-2.83; P ¼ 0.004), acute GVHD (2.57, 1.72-3.84; Po0.001), and CML (0.38, 0.21-0.69; P ¼ 0.002). We should be careful in interpreting results of this smallsized retrospective study; however, reduced regimenrelated toxicity might contribute to better survival in RIST. The low relapse rates following RIST suggest a strong antitumor activity through allogeneic immunity. Bone Marrow Transplantation (2005) 36, 667-674. doi:10.1038/sj.bmt.1705122; published online 22 August 2005 Keywords: allogeneic hematopoietic stem-cell transplantation; regimen-related toxicity; graft-versus-host disease; nonrelapse mortality; graft-versus-leukemia effect Allogeneic hematopoietic stem-cell transplantation (autologous stem-cell transplantation (allo-SCT)) is a therapeutic option for advanced hematologic malignancies. A small but significant proportion of these patients can be cured with allo-SCT. 1 Conditioning regimens have been developed to maximize dose intensity, escalating the dose-limiting toxicity in nonhematopoietic tissues. 2 Conventional stem-cell transplantation (CST) using a myeloablative preparative regimen is associated with severe regimen-related toxicities (RRT), resulting in high nonrelapse mortality (NRM) especially for old patients. 3 NRM tends to be higher in patients with refractory or advanced diseases, who have been treated heavily, compared with those who have achieved remission. 3 Considering that highdose chemotherapy followed by allo-SCT is ineffective for these patients, 4 and that intensification of preparative regimens usually leads to severe RRT and high NRM, 5 it remains unknown whether myeloablative preparative regimens are beneficial to improve survival of patients with advanced chemorefractory leukemia.A new strategy for transplantation using a reducedintensity stem-cell transplantation (RIST) or...

The changing scene of allogeneic stem cell transplantation for chronic myeloid leukemia—a report from the German Registry covering the period from 1998 to 2004

“…Also, the frequency of severe aGvHD (grade II-IV) was equal in reduced and standard conditioned patients (37% vs. 36%) in this DRST analysis. However, previous reports of similar frequencies of severe GvHD (grade II-IV) of 14%-19% irrespective of the intensity of conditioning [27] are in contrast to other studies where severe GvHD (grade II-IV) was significantly less frequent after reduced conditioning [28].…”

Reduced-intensity conditioning for acute myeloid leukemia: is this strategy correct

“…In a much smaller study, Kojima et al 43 compared 70 patients receiving reduced-intensity versus 137 receiving myeloablative treatment. This comparison was restricted to those aged 50-59 years.…”

Change of the Blood Concentration of Tacrolimus after the Switch from Fluconazole to Voriconazole in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

“…[2][3][4][7][8][9][10][11][12][13][14][15][16] Calcineurin inhibitors are routinely administered as prophylaxis for graft versus host disease (GVHD) in patients receiving allogeneic HSCT (allo-HSCT). [17][18][19] Triazole antifungal agents are metabolized by the cytochrome P450 (CYP) enzyme system, CYP2C9, CYP2C19, and CYP3A4 isozymes, 8,10) whereas the calcineurin inhibitors are primarily metabolized by CYP3A4. 3,8,10,11) Therefore, the triazole antifungal agents competitively inhibit metabolism of the calcineurin inhibitors.…”