Reduced intensity preparative regimens for allogeneic hematopoietic stem cell transplantation: a single center experience

Abstract

Summary:According to recent reports, fast engraftment with minimal transplant-related toxicity and mortality (TRT, TRM) can be achieved by using reduced-intensity preparative regimens in allogeneic hematopoietic stem cell transplantation (HSCT). We report our experience with related (39%) and unrelated (61%) HSCT in 44 high risk patients (AML, ALL, CML, CLL) receiving either busulfan/fludarabine or busulfane/fludarabine/ATG or TBI/fludarabine as reduced-intensity preparative regimens. Organ toxicity was minimal with mild mucositis and no major bleeding. Acute GVHD was recorded in 64% of the patients. Twenty-three patients achieved complete remission after transplantation, and complete chimerism was obtained in all patients with stable engraftment (35 patients). Twenty-nine patients died: 15 due to relapse/progression, 14 due to TRM. Survival with median follow-up of 18.5 months was significantly better in patients with matched related transplants compared to patients with other transplants. However, there was no difference between related and unrelated transplants with regard to engraftment, TRM and GVHD. In conclusion, our results in high-risk patients transplanted in CR or with smoldering leukemia from a related donor are encouraging, although a longer follow-up and a larger group of patients is needed in order to evaluate the role of different reduced-intensity preparative regimens in unrelated and related HSCT. mal procedure-related toxicity 1-3 and to facilitate fast donor cell engraftment, development of donor chimerism 4,5 and generation of graft-versus-leukemia effects. 6,7 Although toxicity is reduced, deaths due to acute and chronic GVHD, as well as infections are observed. There are many preparative regimens 6,7 and most of the reduced-intensity preparative regimens are fludarabine-based conditioning regimens combined with busulfan, 2,8 cyclophosphamide, 3,6,9 melphalan 1,5 or total body irradiation. 10,11 In order to obtain more insight into the feasibility of different preparative regimens we performed allogeneic HSCT randomly using three different fludarabine-based preparative regimens in a group of 44 patients with hematological malignancies not suitable for conventional preparative regimens. These were low-dose busulfan in combination with fludarabine and anti-thymocyte-globulin (Bu/Flu/ATG), Bu/Flu without ATG and 4 Gy total body irradiation in combination with fludarabine (TBI/Flu). Patients and methodsBetween February 1999 and December 2000, 44 patients who had an HLA-matched or mismatched related or unrelated donor as determined by serological typing for HLA-A/B and molecular typing for HLA-DR/DQ, were treated in our center. The most important patient characteristics are depicted in Table 1. Twenty-three were male and 21 female. The age range at the time of transplantation was 20 to 67 years, with a median of 52 years. Twenty-seven patients had AML, five ALL, nine CML and three CLL. Patients with hematological malignancies were included in this study if they were older than 55 years. They wer...

The early referral for reduced-intensity stem cell transplantation in patients with Ph1 (+) chronic myelogenous leukemia in chronic phase in the imatinib era: results of the Latin American Cooperative Oncohematology Group (LACOHG) prospective, multicenter study

“…Our data and that from others indicate that RIST is effective for allografting individuals with CML; [6][7][20][21][22][23][24][25] despite the fact that most studies with reduced-intensity conditioning have a relatively short follow-up, there is information indicating that the procedure has a lower prevalence and severity of GVHD, 26 and similar efficacy to conventional allografting; the low prevalence of chronic GVHD in this study supports this observation, which may be related to the diminished organ damage induced by the conditioning schedule. Since this method is more feasible and affordable for patients and physicians in developing countries, the number of allografts in these places has increased substantially, as well as the publications related to bone marrow transplantation stemming from places where this therapeutic maneuver was considered as unaffordable previous to the development of this technology.…”

“…Other authors have included CML patients in their reports of RIST. 22 The data in this paper indicate that the results of our approach to conduct RIST 4-6 could be reproduced in patients with CML in other developing Latin American countries, specifically Colombia, Venezuela and Brazil. The results in this group of individuals were, as expected, better than those we obtained some years ago, 6 because we have now included only patients in CP; in this context, our results are comparable to those obtained by Or et al 7 in Jerusalem; they found a 5-year OS of 85%, whereas we have found an 830-day probability of survival of 92%; however, it has to be taken into account that follow-up of the patients in this study is still short.…”

“…Allogeneic RIST has been shown to be useful in individuals with CML. 6,7,[20][21][22] We published in 2002 the first series of patients in Me´xico with CML given an RIST; in that group, we included individuals with CP, accelerated and blastic phases. 6 Later, Or et al, 7 they found a 5-year overall survival (OS) of 85%.…”

Graft Versus Host Disease After Stem Cell Allotransplantation With Low-Dose Total Body Irradiation, Fludarabine, and Antithymocyte Globulin

“…ATG has been used in ablative and nonablative transplantation with a variety of grafts (21)(22)(23)(24). The aim of its use is to achieve host immunosuppression and in vivo T-cell depletion.…”

Therapeutic choices in patients with Ph-positive CML living in Mexico in the tyrosine kinase inhibitor era: SCT or TKIs?

“…Allo-SCT has been shown to be useful in individuals with CML; reduced-intensity preparative regimens have been used successfully by us 5,6 and others 4,7,[23][24][25][26][27] and we have elected to use this preparative regimen for financial reasons. 28 Despite the fact that most studies with NST have a relatively short follow-up, there is information which indicates that the procedure has a similar long-term efficacy as that of conventional allografting.…”