scholarly journals One year follow up of 71 leukemic patients who received fludarabine and busulfan (FluBup) as myeloablative conditioning regimen for allogeneic PBSCT

2005 ◽  
Vol 11 (2) ◽  
pp. 21
Author(s):  
M. Iravani ◽  
M. Tavakoli ◽  
A.R. Shamshiri ◽  
A. Mousavi ◽  
B. Bahar ◽  
...  
Keyword(s):  
Conditioning Regimen ◽  
Myeloablative Conditioning ◽  
Allogeneic Pbsct ◽  
One Year

scholarly journals Allogeneic Hematopoietic Cell Transplantation with Myeloablative Conditioning Regimen of Reduced Toxicity Is Associated with Favorable Survival in Patients with Secondary Acute Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Eleni Gavriilaki ◽  
Chrysavgi Lalayanni ◽  
Ioanna Sakellari ◽  
Christos Varelas ◽  
Despina Mallouri ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Transplant Recipients ◽  
Myeloablative Conditioning ◽  
Comorbidity Index ◽  
Reduced Toxicity ◽  
Reduced Intensity

Background: Secondary or treatment-related acute myeloid leukemia (sAML) is associated with poor outcomes. Although allogeneic hematopoietic cell transplantation (alloHCT) is the treatment of choice, patient eligibility criteria and optimal conditioning regimen remain under study. We have previously shown an advantage of a myeloablative conditioning regimen with reduced toxicity (Fludarabine 150mg/m2, Treosulfan 42g/m2, FluTreo) compared to a reduced intensity regimen. However, the long-term effects of this regimen remain unknown, especially in comparison to patients not receiving alloHCT. Aims: We hypothesized that patients transplanted with FluTreo would have a long-term survival advantage over other treatment alternatives. Methods: We retrospectively studied consecutive patients treated for sAML in our center over the last two decades (1998-2018). Exclusion criteria were: age>70 years, ECOG performance status≥3 at presentation, induction regimens≤2, and autologous or haploidentical HCT because these were performed in individual patients. Since 2013, we have introduced FluTreo for patients with a suitable donor that would have been previously eligible only for reduced intensity conditioning/RIC. The following factors were studied in the whole cohort: age, type of disease (treatment-related or post myelodysplastic syndrome/MDS), previous intensive chemotherapy cycles, cytogenetic risk, overall (OS) and disease-free survival (DFS). In transplant recipients, we also recorded HCT-comorbidity index/CI score, cumulative incidence (CI) of graft-versus-host disease (GVHD), and treatment-related mortality (TRM). Follow-up was calculated from diagnosis in the whole cohort; and from date of transplant in the sub-group analysis of transplant recipients. Results: We studied 19 FluTreo recipients compared to 46 recipients of other conditioning regimens (38 myeloablative and 8 RIC), and 52 patients treated only with chemotherapy. Complete remission (CR) had been achieved in all FluTreo recipients before HCT, compared to 53% of other transplants, and 44% of chemotherapy only patients (p<0.001). As expected, median age was increased in FluTreo and chemotherapy only patients (59 and 58 years respectively), compared to other transplants (48 years, p<0.001). There was no other difference in baseline characteristics. With a median follow-up of 43 (range 13-204) months in surviving patients, 4-year OS was 40.3% in FluTreo versus 31.3% in other transplants and 11.8% in chemotherapy only patients (p<0.001, Figure 1A). In the multivariate analysis, achieving CR (p<0.001) and the FluTreo group (p<0.001) were associated with favorable OS, independently of age and cytogenetic risk. 4-year DFS was 32.3% in FluTreo, versus 29.3% in other transplants and 10.2% in chemotherapy only patients (p=0.001, Figure 1B). Within transplanted patients, there was no significant difference in GVHD, relapse and TRM between FluTreo and other transplants. Within the FluTreo group, acceptable rates of CI in severe acute and extensive chronic GVHD were observed (15.2% and 18.4%, respectively). Similarly, 4-year CI of TRM reached 30.4%, despite a median HCT-CI of 3 (0-7), age of 59 (51-67) years, 4 lines of treatment (3-6), and a majority of matched unrelated donors (13/19). Conclusion: Our real-world study confirms that alloHCT with FluTreo expands the transplant population with similar safety and efficacy to previous transplant modalities in sAML patients. Achievement of CR remains a major predictor of OS in these patients. The choice of alloHCT in this unique patient population of a rather older age and comorbidity index needs to be revisited. Figure 1 Disclosures Gavriilaki: Omeros Pharmaceuticals: Consultancy.

Phase II Trial Of Medium-Dose VP-16, Cyclophosphamide and Total-Body Irradiation Conditioning Regimen Before Allogeneic Stem Cell Transplantation For Acute Lymphoblastic Leukemia In Adults

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 544-544
Author(s):  
Tatsunori Goto ◽  
Akio Shigematsu ◽  
Makoto Onizuka ◽  
Shin Fujisawa ◽  
Ritsuro Suzuki ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Once Daily ◽  
High Risk Disease ◽  
Total Body ◽  
One Year ◽  
Medium Dose

Abstract Background The prognosis of adult patients (pts) with acute lymphoblastic leukemia (ALL) is dismal, and allogeneic stem cell transplantation (allo-SCT) is performed in most pts. However, even for pts treated with allo-SCT using the standard regimen of cyclophosphamide with total body irradiation (CY/TBI), the prognosis is not satisfactory due to a high rate of relapse. We previously reported excellent outcomes in adult pts with ALL undergoing allo-SCT conditioned with medium-dose VP-16, CY and TBI (medium-dose VP/CY/TBI). We therefore conducted a prospective nationwide multicenter phase II trial (UMIN trial number 000001672) to evaluate the efficacy of this conditioning regimen. Methods The eligibility criteria of this study were as follows: (1) diagnosis of ALL or acute biphenotypic leukemia (ABL), (2) aged 15-49 years, (3) in CR, (4) first SCT, (5) PS (ECOG) 0-2, (6) intact organ function, and (7) HLA-serologically 6/6 matched donor. Pts with Burkitt leukemia were ineligible for this study. Conditioning regimen consisted of medium-dose VP (15 mg/kg once daily i.v. for two days) and CY (60 mg/kg once daily i.v. for two days) combined with fractionated TBI (total dose: 12 Gy). Stem cell source was limited to bone marrow (BM) or peripheral blood stem cell (PBSC). The primary endpoint of this study was event-free survival (EFS) at one year after SCT, and the events were defined as death or relapse. The expected 1-year EFS was estimated to be 75%, and the threshold 1-year EFS was estimated to be 55%, on the basis of our previous observations. Results Between February 2009 and August 2011, 52 pts were enrolled, and 50 pts met the criteria. Among 50 eligible pts, the median age was 33.5 years (range, 17-49 years), and 15 pts (30%) were over 40. Twenty-three (46%) pts were female. Forty-eight (96%) pts had ALL and 2 (4%) had ABL. Nineteen (38%) pts were Philadelphia chromosome (Ph)-positive. Forty-seven (94%) pts were in first CR at SCT, and 3 (6%) in second CR. Among pts with ALL in first CR (n=45), 38 (84%) had high-risk disease. Twenty-six (52%) pts underwent SCT from a related donor and 24 (48%) from an unrelated donor. Forty (80%) pts received BM and 10 (20%) received PBSC. All pts achieved neutrophil engraftment. The incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) was 38% and 8%, respectively, and that of chronic GVHD was 54%. After 1-year follow-up of the final enrollment (range, 379-1218 days), the 1-year EFS was 76% (95% confidence interval (CI): 62-86%, Figure). One-year overall survival was 80% (95% CI: 66-89%). No pts died within 100 days after SCT and 1-year non-relapse mortality (NRM) was 14% (95% CI: 6-25%). No secondary malignancies were observed during the-follow-up period. The 100-day and 1-year relapse rate was 2% (95% CI: 0-9%) and 10% (95% CI: 4-20%), respectively. The 1-year EFS for pts with high-risk and standard-risk disease was 76% (95% CI: 59-87%) and 71% (95% CI: 26-92%), Ph-positive and negative pts was 79% (95% CI: 53-92%) and 76% (95% CI: 56-88%), and pts over 40 years and under 40 years was 73% (95% CI: 44-89%) and 77% (95% CI: 59-88%), respectively. In univariate analysis, high-risk disease, Ph-positivity and higher age were not significant risk factors for EFS. Conclusions The results demonstrate that the conditioning regimen of medium dose VP/CY/TBI for allo-HCT in adult pts with ALL enable good disease control without increase in NRM, even for relatively high age pts and pts with high-risk disease. A phase III trial comparing this regimen with standard CY/TBI regimen for adult pts with ALL is warranted. Disclosures: No relevant conflicts of interest to declare.

Tumor Control Achieved Despite Loss of Chimaerism in Renal Cell Carcinoma (RCC) Following Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT): A Case Report.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5401-5401
Author(s):  
Giovanna Andreola ◽  
Federica Gigli ◽  
Cristina Rabascio ◽  
Manuela Cazzanti ◽  
Fedro Peccatori ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Conditioning Regimen ◽  
Tumor Control ◽  
Murine Models ◽  
Serological Tests ◽  
Donor Cells ◽  
Allogeneic Pbsct ◽  
Good General Condition ◽  
History Of

Abstract The achievement of a mixed chimaerism, which eventually converts to full donor chimaerism, after a non-myeloablative allogeneic PBSCT, is thought to be responsible for a graft-versus-tumor effect to occur. Preliminary data from murine models and haematological malignancies suggest that anti-tumor response can be obtained despite loss of donor chimaerism but, to our knowledge, no such data exist on solid tumors. On February 2004, V.P, affected by metastatic RCC, already pretreated with a-IFN and Vinorelbine, developed progressive disease in the lung and in the retroperitoneum. On July 2004 she was enrolled in a clinical protocol of reduced conditioning allogeneic PBSCT. Conditioning regimen was the following: fludarabine 30 mg/mq from day −4 to −1, and TBI (2 Gy) on day 0, when she also received 8.53x106 CD34+cells/kg from her sister, HLA-full matched, ABO compatible. aGvHD prophylaxis was performed with micophenolate mofetile 15 mg/kg bid, from day 0 to +27 and cyclosporine (Cys) 5 mg/kg bid, from day −2 to +36, followed by a tapering until +56. Chimaerism evaluation, performed on day +28 and +56, showed a full donor engraftment (>90% donor cells) on bone marrow (BM) samples, with 78% of donor CD3+ T cell on peripheral blood (PB). During follow-up, no signs of aGvHD were observed and CMV p65 and PCR remained negative. On day +90, peripheral pancitopenia occurred: WBC-190/mm3, PLT-8000/mm3, Hb-7.5 g/dL, associated with marrow aplasia. Chimaerism evaluation on both BM and PB showed a graft failure, (>95% recipient cells); serological tests were negative (HCV, parvovirusB19, EBV, CMV and adenovirus), no history of drug interaction could be identified. Because of febrile neutropenia she started a large spectrum antibiotic therapy, G-CSF 5 mg/die and an immunosuppressive therapy with metilprednisolone 1mg/kg plus Cys 5 mg/kg, After 5 days she had recovered the WBC while PLT normalization occurred after 45 days. Cys was continued and stopped at day +210. After a follow-up of 386 days from transplantation, she is still in good general condition, off treatment and with stable disease. On the basis of murine models, the presence of a sustained SD in an otherwise fatal disease, despite loss of graft may suggest the presence of a host-versus-graftimmune response able to promote anti-tumor responses and may promote the development of novel transplant strategies without the risk of GVHD.

Effect of Graft Source and Transplant Conditioning Regimen Intensity On the Outcomes of Allogeneic Hematopoietic Cell Transplantation for Refractory Mantle Cell Lymphoma (MCL): A Cibmtr Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 815-815
Author(s):  
Mehdi Hamadani ◽  
Wael Saber ◽  
Jeanette Carreras ◽  
Kwang W Ahn ◽  
Ginna G Laport ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Peripheral Blood ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Refractory Disease ◽  
Myeloablative Conditioning ◽  
Heavily Pretreated ◽  
Reduced Risk

Abstract Abstract 815 Introduction: MCL is incurable with conventional chemotherapies and generally follows an aggressive clinical course. After first relapse, the prognosis of refractory MCL is poor with a median survival of approximately 1–2 years. The role of allogeneic hematopoietic cell transplantation (allo-HCT) and the optimal intensity of conditioning regimen for chemotherapy refractory MCL is not known. Methods: We report here the outcomes of allo-HCT in patients with chemorefractory MCL, according to the intensity of transplant conditioning regimens, using the CIBMTR database. The study population included all patients with chemorefractory MCL receiving an allo-HCT reported to the CIBMTR between 1998 and 2010. Patients with evidence of chemosensitive disease at the time of allo-HCT were excluded. Primary outcomes were non-relapse mortality (NRM), progression/relapse (P/R), progression-free survival (PFS), and overall survival (OS). The outcomes of patients undergoing myeloablative conditioning (MA) were compared with those of patients receiving reduced intensity/non-myeloablative conditioning (RIC/NST). Conditioning regimen intensity was defined according to CIBMTR criteria. Results: A total of 74 patients received MA, and 128 underwent RIC/NST. Median follow up of survivors for MA and RIC/NST groups was 35mos and 43mos, respectively. Completeness of follow up at 3 years was 80%. The RIC/NST cohort was older compared with MA cohort (median age 59 yrs vs. 54 yrs, respectively; p<0.001). No significant differences at baseline were observed between the MA and RIC/NST groups in terms of disease stage at diagnosis, B-symptoms, bone marrow or extranodal involvement, disease bulk, central nervous system involvement, disease status at transplantation (primary refractory disease vs. refractory at relapse) and graft type (bone marrow vs. peripheral blood). Significantly more patients in the RIC/NST group had a prior history of undergoing an autologous-HCT (33% vs. 13%; p=0.004), received rituximab therapy prior to transplantation (41% vs. 15%; p0.01) and underwent unrelated donor (URD) allo-HCT (68% vs. 32%; p<0.001) (Table 1). Patients in the RIC/NST group were also more heavily pretreated (p=0.02). Cumulative incidence of grade II-IV acute GVHD at day +100 was 36% and 37% in MA and RIC/NST groups (p=0.93), respectively. Cumulative incidence of chronic GVHD at 1 year post transplantation in similar order was 35% and 43%, respectively (p=0.35). On univariate analysis, at 3 years, comparing MA allo-HCT with RIC/NST allo-HCT no significant differences were found in terms of NRM (47% vs. 43%; p=0.68), R/P (33% vs. 32%; p=0.89), PFS (20% vs. 25%; p=0.53), and OS (25% vs. 30%; p=0.45), respectively. On multivariate analysis, receiving a bone marrow allograft (compared to a peripheral blood graft) and GVHD prophylactic strategies consisting of ex-vivo T-cell depletion or CD34+ selection (compared to tacrolimus-based GVHD prophylaxis) were associated with an increased risk of NRM and inferior PFS and OS. On multivariate analysis higher intensity conditioning was not associated with reduced risk of NRM, R/P or better PFS and OS. Conclusions: Despite a refractory disease state, a small subset of chemotherapy refractory MCL patients can attain durable remissions after allo-HCT. T-cell replete, peripheral blood products appear to be the optimal graft source in refractory MCL patients undergoing allo-HCT. Compared to a more heavily pretreated RIC/NST cohort, MA allo-HCT in refractory MCL patients, was not associated with a reduced risk of relapse or improved survival. Disclosures: No relevant conflicts of interest to declare.

Efficacy and Safety of Unrelated Cord Blood Transplantation in Patients with Acquired Refractory Aplastic Anemia: A Phase II Study on Behalf of Eurocord and the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2671-2671 ◽  
Author(s):  
Régis Peffault de Latour ◽  
Sylvie Chevret ◽  
Charlotte Jubert ◽  
Anne Sirvent ◽  
Claire Galambrun ◽  
...  
Keyword(s):  
Phase Ii ◽  
Research Funding ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Blood Transplantation ◽  
Grade Ii ◽  
One Year

Abstract Background: While therapeutic outcomes in patients (pts) with acquired severe aplastic anemia (SAA) has greatly improved in recent years, results remain poor for pts who are refractory to first-line immunosuppressive therapy (IST) and lack a matched unrelated donor. We conducted a prospective multi-center phase II uncontrolled trial to assess the efficacy and safety of cord blood transplantation (CBT) in refractory SAA pts (NCT 01343953). Patients and methods: Pts with SAA refractory to IST with anti-thymocyte globuline (ATG) and ciclosporin (CsA) were eligible in case of no existing matched unrelated donor but available one or two unrelated CB units containing alone or both together more than 4 x 107/Kg frozen nucleated cells/Kg (no more than 2 out of 6 HLA mismatches allowed between each CB unit and the pts). Pts with isolated bone marrow cytogenetic abnormality (absence of morphologic evidence of myelodysplastic syndrome) were also eligible. The conditioning regimen consisted of fludarabine 30mg/m2 (D-6 to D-3), cyclophosphamide 30mg/kg (D-6 to D-3), ATG (thymoglobulin) 2.5mg/kg at D-3 and D-2 (5mg/Kg total dose) and total body irradiation (2 Gray) on D-2. All pts received one injection of anti-CD20 (150 mg/m2) to prevent EBV reactivation (D+5). CsA was given alone as prophylaxis for graft versus host disease (GVHD). The trial used the Fleming's Single Stage Phase II Design, with sample size computed to demonstrate an improved overall survival (OS) rate at one year from 20% up to 50%, with type I and type II error rates set at 0.05. A minimum sample of 25 pts was required, with a minimum number of 9 pts alive at one year needed to indicate treatment efficacy. Secondary endpoints included cumulative incidences (CumI) of engraftment, acute and chronic GVHD (aGVHD and cGVHD), infections, relapse and late cause of death. Results: 29 pts were included between June 2011 and October 2015. One pt was diagnosed with dyskeratosis congenita and a matched unrelated donor was identified for another pt between inclusion and anticipated date of CBT (exclusion criteria). One pt died before CBT due to a septic shock (D+4 after inclusion). Analyses were conducted in the remaining 26 pts. Median time between SAA diagnosis and CBT was 12 months (interquartile range (IQR) 8.7 to 17.8). All pts received at least one course of IST before CBT (2 courses, n=8). Twenty-three pts received 20 or more transfusions before CBT. BM karyotyping showed 2 pts respectively with monosomy 7 in 4 and 15 mitoses as well as one pt with trisomy 8 in 4 mitoses before CBT. Eight pts (31%) have a PNH clone (median 4.5% [IQR: 3.1-9.7]). Median age at time of CBT was 16 years (IQR 8.25 to 23) and median follow-up is 13.2 months (IQR 4.1 - 23.5). Three out of 26 pts incorrectly received twice the dose of ATG (10mg/Kg total dose) due to protocol violation. Sixteen pts received one CB and 10 received two CB units. Median number of nucleated cells infused was 3.7 x 107/Kg (IQR, 3-4.9) and CD34+ cells infused was 1.4 x 105/Kg (IQR, 1.0-1.9). Myeloid engraftment occurred in 23 pts, with a 60 day-CumI of neutrophil engraftment of 88.5% with full chimerism for all of them. Three pts did not engraft (2 deaths at D71 and D92 and one successful second HSCT). The 100 day-CumI of grade II-IV acute GVHD was 40% (95% CI, 20-60) (8 grade II; 0 grade III; 2 grade IV). Among the 23 pts alive at day 100, five developed cGVHD leading to a one-year CumI of cGVHD at 27% (95% CI, 7-47) (severe cGvHD in 2 pts). During follow-up, 8 pts experienced a total of 18 grade III infections with a 6-month CumI of 32% (95% CI, 13-51). None of the pts presented post-transplant EBV-related lymphoproliferative disorder. Immune reconstitution is shown in Figure 1. Three pts died before 1 year due to non-engraftment (n=2) and infection (n=1, one of those who received twice the dose of ATG). With 23 pts alive at 1 year, the primary objective of the study was thus reached. The one-year treatment related mortality (TRM) was 15% (95%CI, 4-35). One additional pt who had also received twice the dose of ATG died (severe cGvHD) after one year (at 13.6 months), resulting in a 14-month OS of 81% (95%CI, 66-100) (Figure 2). Conclusion: CBT with at least 4 x 107/Kg frozen nucleated cells/Kg after a FLU-CY-TBI-ATG conditioning regimen gave rise to very encouraging results in this particular high risk SAA refractory population. Pediatric and young adult SAA pts who are refractory to first-line IST should now be considered either way for matched unrelated donor or CBT. Disclosures Peffault de Latour: Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding; Amgen: Research Funding.

Follow up of Hemopoietic Chimerism in Individuals Given Allogeneic Hemopoietic Stem Cell Allografts Using an Immunosuppressive, Non-myeloablative Conditioning Regimen: a Prospective Study in a Single Institution

2002 ◽  
Vol 43 (7) ◽  
pp. 1509-1511 ◽  
Author(s):  
Guillermo J. Ruiz-Argüelles ◽  
Briceida López-Martíneza ◽  
Ma. Rayo Santellán-Olea ◽  
Glexsy Abreu-Díaz ◽  
Virginia Reyes-Núñez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prospective Study ◽  
Conditioning Regimen ◽  
Hemopoietic Stem Cell ◽  
Single Institution ◽  
Myeloablative Conditioning ◽  
A Prospective Study

Long Term Follow up of Two Randomized Trials on Antithymocyte Globulin (ATG) for GVHD Prophylaxis in Unrelated Donor Transplants: Chronic GVHD, Bronchiolitis and Quality of Life.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 438-438
Author(s):  
Andrea Bacigalupo ◽  
Maurizio Vignola ◽  
Teresa Lamparelli ◽  
Paolo Bruzzi ◽  
Stefano Guidi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Antithymocyte Globulin ◽  
Randomized Trials ◽  
Chronic Gvhd ◽  
Prospective Trial ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
One Year

Abstract Background . We have reported that rabbit antithymocyte globulin (ATG Sangstat-Genzyme) prevents acute and chronic graft versus host disease (GvHD) in patients undergoing an unrelated donor transplant (Blood2001; 98 (10): 2942–2947). Patients had entered two consecutive randomized trials: in trial-1, 54 patients were randomized to non-ATG (n=25) or 7.5mg/kg rabbit ATG (n=29). In trial-2, 28 patients were randomized in the non-ATG arm and 27 in the ATG 15mg/kg arm. Aim of the study: to assess the risk of extensive chronic GvHD, bronchiolitis obliterans , quality of life, survival and transplant related mortality (TRM) 4 years later. Patients. Seventy five patients survived 100 days after BMT, and were available for analysis : in trial-1 there were 20 patients per arm, in trial-2 there were respectively 18 and 17 patients. The median follow up was 7.4 years for trial-1 and 5.3 years for trial-2. Each patients was updated and assessed for survival, chronic GvHD, for bronchiolitis , relapse of the original disease and quality of life. Results. Results are given in percentage, in the order non-ATG vs ATG patients. At last follow up chronic GvHD (limited+extensive) was scored in 74% vs 33% respectively for non-ATG and ATG of patients in trial 1 (p=0.01) and in 61% vs 29% in trial-2 (p=0.06): when the two trials are combined cGvHD is scored in 68% vs 31% of non-ATG vs ATG patients (p=0.002). Extensive chronic GvHD was scored in both trials in 35% and 13% of patients (0.03). Bronchiolitis was present at last follow up in trial-1 in 50% vs 0% (p=0.01), and in 33% vs 8% in trial-2 (p=0.1). Combined data show bronchiolitis in 40% vs 4% of non-ATG vs ATG patients (p=0.002). Median timing of bronchiolitis was 1155 days. When patients developed bronchiolitis, the mortality was high (50%). Quality of life was assessed by looking at proportion of patients with Karnowski score of 100% at last follow up: the proportion was 37% vs 91% patients in trial-1 (p=0.02), it was 75% vs 100% patients in trial-2 (p=0.2) and overall in 56% vs 95% of all non-ATG vs ATG patiens (p=0.007). Relapse related deaths were 13% in the non-ATG and 11% in the ATG group. Survival: the actuarial survival at 5 years in trial-1 is 48% vs 53% (non-ATG vs ATG) and in trial-2 30% vs 41%. The actuarial TRM is 48% vs 40%, and in trial-2 it is 62% vs 47% (non-ATG vs ATG patients). Actuarial 5 year TRM in patients surviving one year (late TRM) is 28% vs 4% (p=0.02). Conclusions. This updated analysis of two randomized GITMO trials, confirms with longer follow up, that ATG pre-transplant produces (1) a significant reduction of chronic GvHD (from 68% to 31%) and (2) a significant reduction of extensive chronic GvHD (from 35% to 13%). As a consequence quality of life is significantly improved in ATG patients. This study also shows that ATG reduces the risk of chronic bronchiolitis (from 40% to 4%), and late TRM (beyond one year) (from 28% to 4%). These data give strong support for the inclusion of ATG in the conditioning regimen of unrelated transplants: dosing and timing should be considered (Blood2003; 102 (11); 242a) and could be tested in a prospective trial. This work was supported by Fondazione CARIGE, GENOVA

Unrelated Cord Blood Transplantation Using Myeloablative Conditioning Regimen for Adults with Acute Myeloid Leukemia in First Complete Remission. A Survey by EUROCORD and the Acute Leukemia Working Party of the EBMT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 836-836
Author(s):  
Annalisa Ruggeri ◽  
Myriam Labopin ◽  
Guillermo Sanz ◽  
Josep-Maria Ribera ◽  
Anne Sirvent ◽  
...  
Keyword(s):  
Median Time ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Myeloablative Conditioning ◽  
Grade Ii ◽  
First Complete Remission ◽  
Grade Iii ◽  
Acute Myeloid

Abstract Abstract 836 Patients with high-risk acute myeloid leukemia (AML) have few chances of cure without allogeneic hematopoietic stem cell transplantation (HSCT). HSCT can be used in first remission to cure patients with poor-risk cytogenetics, or as rescue for patients refractory to chemotherapy. Umbilical cord blood (UCB) is one acceptable stem cell source for adult lacking a suitable HLA matched donor. We retrospectively analyzed 134 adults (>18 years) with de novo AML in first complete remission (CR1), who received UCBT as first transplant after a myeloablative conditioning regimen (MAC). Patients were transplanted from 2000–2010 in EBMT centers. Median age at UCBT was 33 years (range 18–63) and median weight was 65 Kg (range 46–112). Based on available cytogenetic and molecular markers at diagnosis (n=111) 45% of patients were classified in the intermediate risk and 31% in unfavorable risk group. Twenty six patients had a FLT3/ITD-positive mutation status. The median time from diagnosis to UCBT was 5.9 months, and the median duration of remission prior to transplant was 104 days. Grafts were composed of 1 (sUCBT) (n=100) or 2 (dUCBT) (n=34) CB units. Thirty two percent of CB units were identical to recipient or had 1 HLA disparity (antigen level for HLA-A and B allelic level for DRB1), while 68% had 2–3 HLA disparities. Median TNC cell dose at infusion was 2.7×10^7/kg in sUCBT and 3.9×10^7/kg in dUCBT.All patients were transplanted using a MAC, from which 60% were busulfan based (n=80). The most frequent regimens used were busulfan+fludarabine+thiotepa (n=56) and cyclophosfamide+TBI12Gy+fludarabine (n=40). ATG was used as part of the conditioning regimen in 73% of patients. GVHD prophylaxis consisted either of CSA ± MMF or CSA ± steroids in 45% and 32% of patients, respectively. Overall, the median follow-up was 22 months (range 3–120), (median follow up 28 months for sUCBT and 22 months for dUCBT). The cumulative incidence (CI) of 60 days neutrophil recovery was 90 ± 3%, (median time of 23 days) and it was 87% for sUCBT and it was 90% dUCBT.At day 100, chimerism test showed full donor chimerism in 92% of patients (data available for 70% of patients who engrafted). At day 100, CI of acute GVHD (grade II–IV) was 19 ± 3%. and it was 12% and 38% for patients transplanted with sUCBT and dUCBT, respectively (p=0.001). Among 34 patients who received a dUCBT, 14 experienced grade II–IV acute GVHD (grade II (n=10), grade III (n=3), grade IV (n=1)) and of those transplanted with a sUCBT, 10 out of 17 had grade II, 4 had grade III, and 3 grade IV. CI of chronic GvHD at 1 year was 20 ± 3%. CI of TRM at 1 year was 32 ± 3%. In the multivariable analysis, TNC dose at infusion >2.9×10^7/kg (p=0.02) was associated with decreased TRM, however in spite of higher incidence of aGVHD dUCBT was not associated with higher TRM. Fifty eight patients died. The causes of death were infection, other transplant-related events (n=45) or relapse (n=13). CI of 2y relapse was 16 ± 4%. It was 15% for those patients transplanted with sUCBT (n=100) and 18% with dUCBT (n=34). Out of 26 patients FLT3/ITD positive, 7 relapsed at a median time of 96 days after UCBT. The 2y probability of leukemia-free-survival (LFS) was 52 ± 2%. There was a trend towards a higher LFS in patients with a longer duration of remission (>66 days, 27% versus 61%, p=0.07). In multivariable model, the use of busulfan in conditioning regimen (HR 2.2, p=0.006) and the use of double UCBT (HR 1.9, p 0.06) were independently associated with better LFS. In fact, LFS was 58% for those patients receiving Busulfan based compared to 42% receiving a TBI based, and it was 58% for dUCBT and 50% for sUCBT. In conclusion, UCBT using one or two CB units is a valid treatment option for adults with high risk AML in CR1 without an HLA identical donor. The best conditioning regimen for single or double UCBT has to be assessed in prospective clinical trials. Disclosures: No relevant conflicts of interest to declare.

The Curative Potential Of Fludarabine125, Melphalan100, and Busulfan4 As a Conditioning Regimen For Myeloid Malignancies Of Elderly Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4551-4551
Author(s):  
Tomoaki Ueda ◽  
Aki Sato ◽  
Kazuya Sakai ◽  
Hiroyuki Muranushi ◽  
Yusuke Okamoto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Elderly Patients ◽  
Relapse Rate ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Myeloid Malignancies ◽  
Gvhd Prophylaxis ◽  
One Year

Introduction The prognosis of elderly patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is poor, even in the patients who achieved good response after induction therapy. In order to undertake allogeneic stem cell transplantation (allo-SCT) with reduced toxicity and without total body irradiation (TBI), we conducted a combination regimen consisted of fludarabine, busulfan, and melphalan (Flu/Mel/Bu) for reduced intensity stem cell transplantation (RIST) conditioning. Patients and methods Among a total of 50 patients who underwent Flu/Mel/Bu conditioning between 2004 and 2012 in our institute, 32 patients with myeloid malignancies were retrospectively reviewed. Disease status was defined by WHO classification 2008. Therapy consisted of fludarabine 25 mg/m2 for five days (125mg/m2) and melphalan 50mg/m2 for two days (100mg/m2), both by intravenous infusion. Busulfan 2 mg/kg was administered orally for two days (4mg/kg) between 2004 and 2006, and intravenously at 1.6 mg/kg for two days (3.2mg/kg) between 2007 and 2012. Results Among the 32 eligible patients, 18 were female and 14 male. Seventeen patients were diagnosed with AML, 14 with MDS and one with chronic myelomonocytic leukemia (CMML). Median age was 59 years (32-66 years), and the median follow-up period was 1337 days (12-3043 days).Disease status of AML was complete remission (CR)1 (5), CR2 (10), CR3 (1) and CR4 (1), respectively, and all CR1 patients had poor risk factors. Disease status of MDS was RA (4), RARS (2), RCMD (1), RAEB-1 (5) and RAEB-2 (2), respectively. Three patients of RAEB conducted induction chemotherapy and two patients achieved CR. Donor sources consisted of 22 of unrelated bone marrow (URBM), 5 of related bone marrow (RBM), 3 related peripheral blood (RPB), and 2 of unrelated cord blood (URCB), respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus plus short term methotrexate (TAC+sMTX) (25) and cyclosporin plus methotrexate (CsA+sMTX) (7). The cumulative incidence of grade II-IV acute GVHD was 31.7% and chronic GVHD was 85.9%. Five-year non-relapse mortality (NRM) was 15.9% and the 5-year relapse rate was 18.8%. One-year overall survival (OS) was 81.2% (95%CI 62.9-91.1), 5-year OS was 74.6% (95%CI 55.5-86.4), one-year progression free survival (PFS) was 78.1% (95%CI 59.5-88.9), 5-year PFS was 65.4% (95%CI 44.2-80.2). Fourteen patients were older than 60 years, and both 5-year OS and PFS of this group were 85.7% (95%CI 53.9-96.2). For AML, one-year OS was 82.4% (95%CI 54.7-93.9), 5-year OS 70.1% (95%CI 42.3-86.3), one-year PFS was 76.5% (95%CI 48.8-90.4) and 5-year PFS was 61.8% (95%CI 32.9-81.2). Five-year NRM was 11.8% and the 5-year relapse rate was 26.5%. For MDS, both one-year OS and 5-year OS were 78.6% (95%CI 47.2-92.5), and both one-year PFS and 5-year PFS were 69.8% (95%CI 37.8-87.6). Five-year NRM was 21.4% and the 5-year relapse rate was 8.7%.On the other hand, we conducted 32 allo-SCT for myeloid malignancies (22 of AML in CR and 10 of MDS) with conventional conditioning regimens of cyclophosphamide (Cy) and TBI or Bu and Cy between 2004 and 2012. Median age was 36.5 years (20-54 years), and the median follow-up period was 1191 days (38-3366 days).Disease status of AML was CR1 (14), and CR2 (8), respectively. Disease status of MDS was RA (3), RARS (2), RCMD (1), RAEB-1 (4), RAEB-2 (1), and MDS-U (1), respectively. Four patients of RAEB conducted induction chemotherapy and achieved CR. Donor sources were URBM (15), RBM (11), CB (5) and RPB (1), respectively. GVHD prophylaxis consisted of TAC+sMTX (17) and CsA+sMTX (15).The outcomes of Flu/Mel/Bu were not statistically inferior to those of conventional regimens with one-year OS of (81.2% vs. 87.1%, p=0.564) and 5-year OS of (74.6% vs. 78.0%, p=0.564), and one-year PFS of (78.1% vs. 83.9%, p=0.183) and 5-year PFS of (65.4% vs. 80.4%, p=0.183). Conclusions Flu/Mel/Bu was tolerable, and produced good outcomes and may be a candidate for curative conditioning regimen of RIST, especially for patients with myeloid malignancies in controlled status. Disclosures: No relevant conflicts of interest to declare.

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