scholarly journals A fludarabine-based dose-reduced conditioning regimen followed by allogeneic stem cell transplantation from related or unrelated donors in patients with myelodysplastic syndrome

2001 ◽  
Vol 28 (7) ◽  
pp. 643-647 ◽  
Author(s):  
N Kröger ◽  
J Schetelig ◽  
T Zabelina ◽  
W Krüger ◽  
H Renges ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Myelodysplastic Syndrome ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donors

Allogeneic Stem Cell Transplantation from Unrelated Donors after Reduced Intensity Conditioning in Patients with MDS/sAML. A Report from the Chronic Leukemia Working Party (CLWP) of the EBMT.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5176-5176 ◽  
Author(s):  
Nicolaus Kroeger ◽  
Ronald Brand ◽  
Rodrigo Martino ◽  
Philippe Guardiola ◽  
Anja van Biezen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Working Party ◽  
Stem Cell Source ◽  
Unrelated Donors

Abstract We analysed the results of 67 patients with MDS/sAML who were transplanted with allogeneic stem cell transplantation from unrelated donors after a reduced intenisity conditioning and reported to the EBMT. The median age was 52 years (range 17–70 years) and stem cell source was bone marrow (n = 30) or peripheral blood progenitor cells (n = 33).. The graft was HLA matched in 57 patients while 8 patients received SCT from HLA-mismatched donor. The MDS classification was as follows: RA/RARS: n=8, RAEB/CMML: n = 14, RAEB-t/sAML: n = 22. The conditioning regimen consisted of fludarabine/busulfan (n=15), fludarabine/melphalan (n=6), fludarabine and TBI (n=8) or fludarabine and others (n=36)At time of transplantation only 12 (18%) were in first complete remission. The Kaplan-Meier estimates of the probability of 2 years overall and disease free survival were 33 % (95% CI: 21–45 %) and 24 % (95% CI: 12–36 %), respectively. The probability of relapse at two years was 58 % (95% CI: 40–76 %) and of one year treatment-related mortality 37 % (95% CI %: 23–51 %). In an univariate analysis assessing source of stem cells, age, disease type, T-cell depletion, and HLA-matching no factor was significant for OS, EFS, TRM and Relapse. Allogeneic stem cell transplantation after a reduced intensified conditioning followed by unrelated SCT seems to be a feasible approach in those patients who were no candidates for a standard conditioning but is associated with a considerable number of relapses.

Reduced intensity allogeneic stem cell transplantation in patients with myelodysplastic syndrome: Does the conditioning matter? A retrospective study of the SFGM-TC on 61 patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6547-6547
Author(s):  
L. Terriou ◽  
Z. Chir ◽  
H. Esperou ◽  
J. Boiron ◽  
N. Gratecos ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Myelodysplastic Syndrome ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Immunosuppressive Treatment ◽  
Conditioning Regimen ◽  
The Impact ◽  
Reduced Intensity

6547 Background: Reduced-intensity allogeneic stem cell transplantation (RIT) has emerged as an alternative to myeloablative transplantation in pts with myelodysplastic syndrome (MDS). Given the uncertainty regarding the appropriate conditioning, SFGM-TC conducted a retrospective multicenter study with the attempt to evaluate the impact of conditioning on pts’ outcome. Methods: The record of 61 pts (37 males) with MDS who received a RIT between 1998 and 2003, from 22 French transplantation centres, were reviewed. According to the FAB classification, 11 pts had RA at diagnosis, of whom one had progressed to REAB and one to AML before transplantation. Thirty-two pts had REAB, of whom 2 had progressed to REAB-T and 7 to AML. Twelve pts had REAB-T and 6 CMML, of whom 8 progressed to AML. The median time from diagnosis to RIT was 12 months (6–129). Conditioning regimen consisted of fludarabin (Flu) plus busulfan ( n=29), Flu plus 2-Gy TBI ( n=20) and idarubicin plus aracytine and Flu (n=12). Donors were HLA-identical siblings (n=52) and HLA-matched unrelated (n=9). All pts received peripheral blood stem cells. The median of CD34+ infused cell dose was 5 × 106/kg (0.5–17.3). Results: At the reference date of 1 July 2005, median follow-up was 44.7 months (21–85). Estimated 3-year overall survival (OS), progression free survival (PFS), relapse and transplant-relapse mortality (TRM) were 35%, 27%, 66% and 30%, respectively. Neither of the 3 conditioning regimens used had impact on pts’ outcome. In multivariable analyses, while acute III/IV grade GVHD development was the only factor found to adversely influencing OS (HR=3.6; 95% CI: 1.1–12.2), chronic GVHD development was the only favourably influencing PFS and relapse ratios (HR=0.3; 95% CI: 0.1–0.7 and HR=0.2; 95% CI: 0.1–0.6, respectively). TRM was adversely influenced by male sex of pt (HR=9.2; 95% CI: 1.5–66.6). Conclusions: RIT seems to be an effective treatment in MDS pts irrespective of conditioning type. While acute III/IV grade GVHD appeared to be detrimental, the benefit effect of chronic GVHD was to be bound to GVL effect. New approaches with focus on immunosuppressive treatment are needed to enhance the GVL effect with an acceptable risk of GVHD. No significant financial relationships to disclose.

A Fludarabine-Based Non-Myeloablative Conditioning Regimen in Allogeneic Stem Cell Transplantation from Related and Unrelated Donors in Chronic Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5372-5372
Author(s):  
Yi Luo ◽  
He Huang ◽  
Zhen Cai ◽  
Yamin Tan ◽  
Xiaoyan Han
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Conditioning Regimen ◽  
Chronic Phase ◽  
Myeloablative Conditioning ◽  
Unrelated Donors

Abstract Objective: To evaluate the efficacy and safety of a fludarabine-based non-myeloablative conditioning regimen in allogeneic stem cell transplantation (SCT)from related and unrelated donor for chronic myeloid leukemia in chronic phase(CML-CP). Methods: Fifteen consecutive patients with CML-CP between May, 2005 and July, 2006 were treated with a single non-myeloablative conditioning regimen in this study. They were 10 males and 5 females with a median age of 41 years (range, 18–49). Donors were HLA-A, B and high resolution DR fully matched siblings (n=8), matched unrelated donors (n=6), and 1-locus mismatched unrelated donors (n=1). The stem cells were collected from either peripheral blood (n=9) or bone marrow (n=6). The conditioning regimen included fludarabine 30 mg/m2/day (days -10 to -5), oral busulfan 4 mg/kg/day (n=4 patients), or intravenous busulfan 3.2 mg/kg/day (n=11 patients) (days -6 to -5) and anti-thymocyte globulin (Fresenius, Germany) (5mg/kg/day) (days -4 to-1). Mycophenolate mofetil combined with cyclosporin A and methotrexate was used for prevention of acute graft-versus-host disease(GVHD) after transplantation. Lipoprostagandin E1 was used in prophylactic regimen for hepatic veno-occlusive disease(VOD). To assess engraftment, degree of chimerism, minimal residual disease and relapse, all patients were monitored by cytogenetic analysis and donor vs host-specific DNA markers using short tandem repeats (STR) assay. The average cell number of MNC transfused was 4.83 (3.14~11.5)×108/kg; CD34+ cells were 3.47(2.38~6.24)×106/kg, CFU-GM was 2.15 (1.85~3.06) ×105/kg. Results: Engraftment of neutrophils and platelets was achieved in 14 out of 15 (93.3%) patients within a median of 13 days (range, 8–21) and 18 days (range, 10–35), respectively. Fourteen patients achieved complete donor chimerism in the peripheral blood before day +35 and one developed graft failure. No patients developed acute GVHD and VOD, but one died from interstitial pneumonia while she was in continuous complete remission 2 months following transplantation. With a median follow-up of 5 months (range 1.5 to 15), 13 of them were still in CCR. The overall non-relapse mortality in this group was 6.67% (1/15 patients). Overall survival, and disease-free survival rates were 93.3% and 86.7%, respectively. Conclusion: A fludarabine-based non-myeloablative conditioning regimen in allogeneic stem cell transplantation from related and unrelated donors is an effective and safe choice for patients with chronic myeloid leukemia in chronic phase.

Intravenous Busulfan-Based Conditioning Prior to Allogeneic Stem Cell Transplantation in Adults Patients with AML - An ALWP-EBMT Survey.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1995-1995 ◽  
Author(s):  
Arnon Nagler ◽  
Myriam Labopin ◽  
Avichai Shimoni ◽  
Donald Bunjes ◽  
Pedro Pimentel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Advanced Disease ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
The Impact

Abstract Oral Busulfan (Bu) is the historical backbone of pre-allogeneic stem cell transplantation (alloSCT) conditioning regimen. However, oral Bu has an erratic and unpredictable absorption with wide inter and also intra-patient (pt) variability. In contrast, I.V. Busulfan (IV Bu) is with more predictable pharmacokinetics and favorable toxicity profile. In order to assess the impact of the use of IV Bu, the ALWP of the EBMT performed a survey in AML pts who received IV-Bu as part of their pre-alloSCT conditioning regimen. 36 EBMT centers participated in this study: 9 centers performed more than 10 transplants each. Overall, 271 alloSCT were analyzed. Age was 44 (range, 16–67) years. 146 were males (54%) and 125 (46%) were females. Disease status at alloSCT was CR1-53%, CR2-16%, primary refractory-13%, Rel1-12%, Rel2-5% and untreated-1%.77% of the pts were with intermediate, 15% with poor and 8% with good risk cytogenetics, respectively. Median WBC at diagnosis was 26×109/L. Conditioning consisted of IV Bu and cyclophosphamide (IV BuCy) in 52%, IV Bu and fludarabine (IV BuFlu) in 38% and various other IV Bu containing regimens in 10% of the pts, respectively. Overall, conditioning was myeloablative in 80% and reduced-intensity (RIC) in 20% of the alloSCT, respectively. Donors were: identical siblings-59%, matched unrelated-28%, mismatched unrelated-10%, mismatched family donors-2%, syngeneic 1%. 83% of the pts were transplanted with mobilized PBSC grafts while 17% received BM grafts. GVHD prophylaxis consisted of CSA and MTX in 85% of the transplants. With median follow up of 24 (range, 1–66) months, 53% of the pts are alive while 47% have died. Day 100 mortality was 7%. The incidence of veno-occlusive disease of the liver (VOD) was 10.4%. VOD was more frequent in pts that were transplanted from unrelated donors in comparison to those who were transplanted from sibling donors (18% vs. 5%, respectively). It was also more common after myeloablative conditioning than RIC (11.5% vs. 5.5%, respectively). Median age of pts with VOD was 42(17–65) years, not different than the age of the whole group, but they had more advanced disease (primary refrectory-35%, Rel2-30%). Day of onset of VOD was +10(range, 1–162). VOD was severe in only 15% of the pts and only 6 pts died of VOD. All together 30% of the pts with VOD are alive. Overall, alloSCT transplant related mortality (TRM) was 22±4% for pts transplanted at CR1 vs 33±8% for pts transplanted at advanced disease. Similarly, leukemia free survival (LFS) for pts transplanted at CR1 was 55±4% vs. 21+5% for pts transplanted in advanced disease. In summary, IV Bu based conditioning reduced the incidence and severity of VOD post alloSCT for AML as compared to published figures for historical controls. A randomized trial assessing VOD incidence and TRM using IV BuCy vs. IV BuFlu with 2 vs. 4 days of IV Bu, respectively may be indicated.

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