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.

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.

Allogeneic Stem Cell Transplantation In Philadelphia Negative Myeloproliferative Or Myelodysplastic/Myeloproliferative Neoplasms: A Retrospective Analysis From The Societe Française De Greffe De Moelle Et De Therapie Cellulaire (SFGM-TC)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3373-3373
Author(s):  
Xavier Cahu ◽  
Patrice Chevallier ◽  
Aline Clavert ◽  
Felipe Suarez ◽  
Mauricette Michallet ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Advanced Disease ◽  
Myeloproliferative Neoplasms ◽  
Thrombotic Event ◽  
Conditioning Regimen ◽  
Adult Patients ◽  
Blast Phase

Abstract Background Philadelphia negative myeloproliferative or myeloproliferative/myelodysplastic neoplasms may evolve towards secondary acute myeloid leukemia (AML). The prognosis of such secondary leukemia is very poor. At present, there are only a few reports assessing the outcome of adult patients with a philadelphia negative myeloproliferative or myeloproliferative/myelodysplastic neoplasm in blast phase (MPN-BP) who received allogeneic stem cell transplantation (allo-SCT). Patients and Methods in this retrospective study, inclusion criteria were: (i) adult patients with a MPN-BP (ii) who received first allo-SCT (iii) between 2000 and 2010 (iv) irrespective of the stem cell source or conditioning regimen. MPN with <20% blasts in blood/bone marrow and AML secondary to myelodysplastic syndromes were excluded from this analysis. Results 60 patients were included. MPN, AML and allo-SCT characteristics are described in table 1. Median age at allo-SCT was 57 (range, 30-68). Patients received allo-SCT in first complete remission (CR1), CR2 or in advanced disease in 22 (37%), 4 (7%) and 34(57%) of cases, respectively. Engraftment was achieved in 55 cases (92%). With a median follow-up of 31 months (range, 25-44), the 3-year overall survival (OS) and Leukemia-Free-Survival (LFS) were respectively 18% and 9%. The 3-year transplant-related mortality (TRM) was 24% whereas relapse incidence was 68%. The 3-year LFS of patients grafted in CR (n=26) was 18% whereas the 3-year LFS of patients allografted in advanced disease (n=34) was only 3% (p=0.008). In the CR group, the 3-year TRM was 24% whereas relapse incidence was 61%. Intermediate or good AML karyotype (3-year LFS of 33% versus 10% for adverse AML karyotype, p=0.03) and the absence of a previous thrombotic event (3-year LFS of 24% versus 0, p=0.02) were associated with an improved LFS in patients allografted in CR. Conclusion These results suggest that the outcome of patients with a MPN-BP is dismal despite allo-SCT due to a high relapse incidence even in patients transplanted in CR. Outside a clinical trial, allo-SCT should be mainly proposed to patients in CR. New strategies are mandatory to improve the outcome of patients in blast phase. Disclosures: No relevant conflicts of interest to declare.

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.

Risk Factors for Outcomes of Family Haploidentical Allogeneic Stem Cell Transplantation for Adults with Acute Leukemias: A Survey on Behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2146-2146
Author(s):  
Fabio Ciceri ◽  
Myriam Labopin ◽  
Vanderson Rocha ◽  
Jacob M. Rowe ◽  
Donald Bunjes ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Advanced Disease ◽  
Disease Status ◽  
Acute Leukemias ◽  
Factors Associated

Abstract Results of family haploidentical allogeneic stem cell transplantation (Haplo-SCT) have been reported from single-center studies as a curative treatment option for patients with high risk acute leukemias. We analysed 273 adult patients with de novo acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) receiving an Haplo-SCT transplanted from 1995 to 2002 in 75 EBMT centers. Overall, 170 AML patients underwent transplantation in CR1 (n=39), CR2 (n=34) or in advanced disease (n=97); median age was 38y (16–70). Overall, 103 ALL patients underwent transplantation in CR1 (n=31), CR2 (n=22) or in advanced disease (n=50); median age was 26y (16–56). Graft composition was based on CD34+ cell selection of PBSC, with median CD34+ cells x106/kg of 7.3 (1.1–45.5) in AML and 8.3 (1.14–30) in ALL. Conditioning regimen was TBI-based in 69% and 87% in AML and ALL respectively. Primary engraftment was documented in 87% AML and in 83% of ALL patients, with ANC 0.5 x109/L in a median of 13 days (8–35) and a 2y probability of PLT > 50 x109/L of 80+/− 5%. The use of TBI was significantly associated with engraftment (90% vs 71%) when adjusting for CD34 dose. The cumulative incidence of acute GvHD >=II was 16% in AML and 15% in ALL. With a median follow-up of 19 months (1–85), the estimated leukemia-free survival (LFS) at 2 years in AML was 39±9%, 33 ±10% and 4±3% and in ALL was 28±9%, 16±8, and 0% for CR1, CR2 and advanced patients respectively. Cumulative incidence using competing risks, for relapse (RI) at 2 y in AML was 8 ±8%, 9 ±9%, 25±8% for CR1, CR2 and advanced; RI in ALL was 27±16% and 41 ±20% in CR1 and CR2. The non-relapse mortality (NRM) at 2 y in AML was 52±18%, 56 ±19%, 69±8% for CR1, CR2 and advanced patients; NRM in ALL was 44±18% and 41±21% in CR1 and CR2. In a multivariate analysis for LFS, advanced disease status at transplant (RR 0.4), ALL (RR 0.5), recipient’s age >33 years (RR 0.4), and absence of TBI in conditioning (RR 0.6) were factors associated with lower LFS. Factors associated with higher transplant-mortality were advanced disease status (RR 2.01), absence of TBI (RR 1.6) and year of transplant<2000 (RR 1.42). Predictive factors for RI were diagnosis of ALL (RR 2.39) and advanced disease (RR 1.96). In conclusion, outcomes of allogeneic transplantation from haploidentical family donors in adults with high risk acute leukaemia are promising and should be considered in the algorithm treatment for patients with an indication of allogeneic SCT lacking an HLA identical donor. Status of the disease, age, type of leukemia and conditioning are some factors associated with outcomes after Haplo-SCT.

Donor Selection for Allogeneic Stem Cell Transplantation In Elderly Patients with Advanced MDS: Younger Matched-Unrelated Donor or HLA-Identical Sibling ?

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 912-912
Author(s):  
Nicolaus Kröger ◽  
Tatjana Zabelina ◽  
Anja van Biezen ◽  
Axel R. Zander ◽  
Theo de Witte
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Disease Status ◽  
Unrelated Donor ◽  
Donor Age ◽  
Matched Unrelated Donor ◽  
Unrelated Donors

Abstract Abstract 912 Allogeneic stem cell transplantation from related and unrelated donors is now a reasonable treatment option for elderly patients with advanced MDS. Retrospective studies have shown that donor age is an independent risk factor for outcome of allogeneic stem cell transplantation. By nature there is a strong correlation between patient's age and age of an HLA-identical sibling. Therefore we investigated whether a young matched unrelated donor should be preferred as donor to an elderly HLA-identical sibling in elderly MDS patients who underwent allogeneic stem cell transplantation. We extracted from the MDS-registry of the EBMT 871 patients who received allogeneic stem cell transplantation between 1986 and 2009 and fulfilled the following criterias: 1. patient's age > 50 years, 2. advanced MDS: RAEB, RAEB-t, CMML or sAML, 3. HLA-identical sibling or fully matched unrelated donor transplantation. From those 871 patients with a median age of 57 years (r., 50–73) 706 received stem cells from an HLA-identical sibling and 168 from a matched unrelated donor, either after standard conditioning (n = 387) or after reduced intensity conditioning (n = 481). After a median follow-up of 30 months, the estimated 3 years overall survival did not differ between patients who received stem cells from HLA-identical sibling or from matched unrelated donor (36 % vs. 34 %, p = 0.8). However, the median donor age was significantly higher for HLA-identical sibling than for MUD transplantation: 56 years (r: 35 – 81 y) vs. 34 years (r: 19 – 64) (p < 0.001). While age as continuous variable did not influence survival in HLA-identical sibling transplantation (HR: 1.002, p = 0.8), but did in MUD transplantation (HR: 1.03, p = 0.009), we performed 4 groups according to donor age: HLA-identical sibling transplantation with donor age > 50 years (n = 535) and donor age 30 – 50 years (n = 169) and matched unrelated transplantation with donor age < 30y (n = 60) and donor age > 30y (n = 107). These groups were well balanced according to disease-status, abnormal cytogenetics, and intensity of the conditioning regimen. The estimated 5 years OS for MUD (donorage < 30y) was 41 % and better than for HLA-identical (donor > 50y) with 31 % (p = 0.03) and HLA-identical (donor 30 – 50 y) with 33 % (p = 0.06), but worse than MUD (donor > 30 y) 24 % (p = 0.003). For overall survival, younger donors (< 30y) remained an independent factor for improved survival in a multivariate Cox model: HR: 0.66 (p = 0.03). Other factors influencing survival were disease status (sAML: HR: 1.31, p = 0.03), standard myeloablative conditioning (HR: 1.40, p = 0.002), and abnormal cytogenetic (HR: 1.26, p = 0.07). In comparison to HLA-identical sibling transplantation the hazard ratio for survival remained less than 1 for matched unrelated donors aged 20–35 years (HR: 0.66–0.99), but the hazard ration increased >1 if matched unrelated donor age becomes greater than 35 years. We conclude that for elderly patients (> 50 years) with advanced MDS who need allogeneic stem cell transplantation a younger unrelated donor should be preferred to an HLA-identical sibling donor. Disclosures: No relevant conflicts of interest to declare.

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