scholarly journals The impact of the age of HLA-identical siblings on mobilization and collection of PBSCs for allogeneic hematopoietic cell transplantation

2010 ◽  
Vol 46 (10) ◽  
pp. 1296-1302 ◽  
Author(s):  
H K Al-Ali ◽  
M Bourgeois ◽  
R Krahl ◽  
E Edel ◽  
S Leiblein ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
The Impact

scholarly journals Allogeneic Hematopoietic Cell Transplantation in AML with Normal Karyotype and NPM1 Mutated FLT3-ITD Negative: A Retrospective Analysis from the Acute Leukemia Working Party of EBMT

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1230-1230
Author(s):  
Ali Bazarbachi ◽  
Myriam Labopin ◽  
Mohamed A Kharfan-Dabaja ◽  
Rainer Schwerdtfeger ◽  
Liisa Volin ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Hematopoietic Cell Transplantation ◽  
Disease Status ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Allogeneic Hct ◽  
Cell Source ◽  
The Impact ◽  
Donor Source

Abstract Background: NPM1 mutation, in the absence of FLT3 internal tandem duplication (FLT3-ITD), confers a survival advantage and lower risk of disease relapse in AML with normal diploid karyotype. The prognostic significance of mutated NPM1 in the setting of allogeneic hematopoietic cell transplantation (HCT) for AML has not been described. Patients and methods: we evaluated the post-transplant outcomes of 156 patients (females=83, 53.2%), median age of 54 (19.5-71) years, with normal diploid karyotype and NPM1 Mutated FLT3-ITD Negative, who underwent an allogeneic HCT between 2006 and 2012. Donor source was limited to matched-related (MRD) or matched-unrelated (MUD) donors, and cell source consisted of bone marrow (BM) or G–CSF mobilized peripheral blood stem cells (PBSC). Patient-, donor-, and disease-characteristics are summarized in Table 1. Results: the median time from diagnosis to allogeneic HCT was 310 (89-3713) days and the median follow-up from time of allografting was 32 (2-86) months. Overall, the 2-year cumulative incidence of relapse (CIR)and non-relapse mortality (NRM) were 27% (20-35) and 13% (8-19) respectively, and the 2-year cumulative incidence of chronic GVHD was 37% (29-46). Finally, the 2-year leukemia-free survival (LFS) and the 2-year overall survival (OS) were 60% (51-68) and 70% (62-77), respectively. In univariate analysis, transplantation in CR1 was associated with lower2-year CIR [CR1=14% (7-23), CR2=37% (23-51), advanced/active=48%(26-67), p=0.0009], superior2-year LFS [CR1=75%(64-86), CR2=51% (36-65),advanced/active=30%(11-49), p<0.0001] and superior2-year OS [CR1=81%(72-91), CR2=67% (54-80), advanced/active=39% (19-59), p<0.0001]. Patients allografted from unrelated donors have higher 100-day cumulative incidence of > grade 2 acute GVHD [MUD=28% (19-39)vs. MRD=12%(5-22), p=0.02]. Patients older than 54.3 years had higher 2-year cumulative incidence of NRM [20% (11-31)vs. 7%[2-14], p=0.03] and inferior 2-year OS [61%(49-72) vs. 78% (68-88), p=0.02]. In multivariable analysis using a Cox proportional-hazard model, transplantation in CR1 resulted in lower2-year CIR and superior2-year LFS and OS. Conclusions: AML disease status at allografting remains the most important predictor of post-allogeneic HCT outcomes despite expression of mutated NPM1. Survival outcomes are better when patients are transplanted in CR1>CR2>advanced/active. The impact of other molecular abnormalities in conjunction with NPM1 is yet to be established. Also, a future matched-controlled analysis comparing AML patients with mutated vs. wild-type NPM1 expression in the setting of allogeneic HCT is warranted. Table 1 variables Results N, (%) Recipient gender F=83 (53%) M=73 (47%) Donor gender F=57 (37%) M=97 (63%) [missing=2] Female donor à male recipient Yes=21 (14%) No=133 (86%) [missing=2] Donor source MRD=66 (42%) MUD=90 (58%) Cell source BM=30 (19%) PBSC=125 (80%) BM+PBSC=1 (1%) Disease status at allogeneic HCT CR1=69 (44%) CR2=64 (41%) Advanced/active=23 (15%) Preparative regimen intensity RIC=85 (54%) MAC=71 (46%) ATG use Yes=84 (54%) No=72 (46%) GVHD prophylaxis CSA+MTX=77 (49%) CSA+MMF=41 (27%) CSA alone=28 (18%) Others=8 (5%) [missing=2] Recipient CMV serology Seropositive =101 (65%) Seronegative =54 (35%) [Unknown/missing=1] Donor CMV serology Seropositive =62 (40%) Seronegative =92 (60%) [Unknown/missing=2] Donor/recipient CMV serology D+/R+=48 (31%) D+/R-=14 (9%) D-/R+=52 (34%) D-/R-=39 (26%) [Unknown/missing=3] Abbreviations : F: female, M: male, MRD: matched-related donor, MUD: matched-unrelated donor, RIC: reduced-intensity conditioning, MAC: myeloablative conditioning, CSA: cyclosporine A, MTX: methotrexate, MMF: mycophenolatemofetil, D: allograft donor, R: allograft recipient Disclosures No relevant conflicts of interest to declare.

scholarly journals Improved Survival in Patients Who Undergo Relapse of Acute Myeloid Leukemia Following Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2014-2014
Author(s):  
Asad Bashey ◽  
Xu Zhang ◽  
Lawrence E Morris ◽  
H. Kent Holland ◽  
Scott R. Solomon ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Cox Model ◽  
Multivariable Analysis ◽  
Hematopoietic Cell ◽  
Time Dependent ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Dismal Prognosis ◽  
Number Of Patients ◽  
The Impact

Relapse of leukemia (RL) is the most common cause of treatment failure following allogeneic hematopoietic cell transplantation (alloHCT) in patients with AML. Historically, patients who suffer RL following alloHCT have had a dismal prognosis. A number of therapeutic options have recently become available for relapsed/refractory AML, including some that are associated with limited toxicity and may be well tolerated in the post-alloHCT setting. These therapies, and advances in supportive care have the potential to prolong survival of recently transplanted patients who suffer RL post post-alloHCT compared to prior cohorts. We hypothesized that patients suffering RL post-alloHCT within the last 5 years will have improved post-relapse survival compared to patients experiencing RL before this period. In order to test this hypothesis, we analyzed 309 patients who underwent a first allo-HCT for AML between Jan 2002 and Dec 2016 at our center and identified 112 patients (36%) who suffered RL post-alloHCT. Data were extracted from our institutional BMT database where they had been prospectively entered. Patient characteristics of those who experienced RL were: median age 53 (19-74); male - 51%; race- white-86%, black 12%, Asian -2%; donor-MRD 33%, MUD 41%, Haplo 26%; graft source - PBSC 86%, BM 11%, CBU 2%, PBSC+BM 1%; regimen intensity - MAC 61%, NST/RIC 39%%; DRI - intermediate 46%, high 50%, v. high 5%; HCT-CI 0-2 (58%), >3 (42%); KPS > 90 (39%) <90 (61%), CMV - pos 70%, neg 29%, year of relapse -2003-2013 (68%), 2014-2018 (32%). Median time from alloHCT to relapse was 170 days (25-1106). Median follow-up of surviving patients was 50 months (15-143). DLI: A first DLI was administered to 19 patients at a median of 41 days post relapse. The corresponding number of patients receiving 2nd, 3rd and 4th DLI were 12, 6 and 2 patients given at a median of 62, 48 and 38 days following the prior DLI. A second alloHCT post RL was performed in 33 patients (29%) at a median of 85 days (22-772d) post relapse using the same donor as the first allo-HCT in 45% and a different donor in 55%. The second transplant was from a MRD, MUD and Haplo donor in 10, 11 and 12 patients respectively. Estimates of post-relapse survival at 1, 2 and 3 years following relapse for all patients are 39%, 23% and 15% (Fig 1). For patients whose AML relapsed between 2003-2013, and 2014-2018 estimated 1, 2, and 3 year survival rates following relapse were 34%, 18% and 9% vs 50%, 32% and 28% respectively (p=0.017, Fig 2). A multivariable Cox model was developed for post-relapse survival considering the following variables: at relapse, gender, race, time from transplant to relapse, donor type, graft source, regimen intensity DRI, HCT-CI, KPS, CMV status, DLI post relapse , second alloHCT post relapse, year of relapse. Second alloHCT post-relapse was tested as a time-dependent covariate. Variables were selected if the p value was less than 0.05. Proportionality was tested for selected variables and all variables passed the test. On multivariable analysis, survival was significantly better for patients who relapsed in 2014-2018 vs patients relapsing in prior years (2003-2013) - HR 0.55. p=0.018. Other variables associated with post-relapse survival were time from BMT to relapse >250 d vs <100 d - HR 0.55, p=0.025 and haplo donor vs MRD for first alloHCT- HR 2.41, p=0.002. The use of DLI or the occurrence of a second alloHCT post-relapse tested as a time-dependent co-variate were not significantly associated with survival in this analysis. These data suggest that survival for AML patients who suffer relapse of malignancy following alloHCT has improved in recent cohorts when compared to historic controls. Approximately one-half and one-third of the patients are now estimated to live 1 and 2 years following relapse and prolonged survival is possible in some cases. The impact of specific interventions that help promote survival following relapse should be further studied Disclosures Solh: ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Amgen: Speakers Bureau.

Impact of Mutations in the Spliceosome Machinery and Ring Sideroblasts in Patients with Myeloid Malignancies Who Received Conventional Chemotherapy or Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1973-1973
Author(s):  
Betty K. Hamilton ◽  
Ali Tabarroki ◽  
Valeria Visconte ◽  
Edy Hasrouni ◽  
Hideki Makishima ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Statistical Significance ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Conventional Chemotherapy ◽  
Myeloid Malignancies ◽  
Ring Sideroblasts ◽  
The Impact

Abstract Abstract 1973 Mutations in the spliceosome machinery have recently been identified in myeloid neoplasms including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and MDS/MPN overlap syndromes. Somatic alterations in SF3B1, U2AF1 and SRSF2 are the most frequently affected spliceosome genes in myeloid malignancies with the frequencies of any of the 3 genes being 39% in low risk MDS, 11% in high risk MDS/AML (primarily U2AF1), and 24% in MDS/MPN, (primarily SRSF2). While SF3B1 mutations as well as ring sideroblasts (RS) appear to be associated with improved survival and lower risk of leukemic evolution, mutations of U2AF1 and SRSF2 appear to be associated with poorer outcomes. Allogeneic hematopoietic cell transplantation (HCT) is the only curative option for many myeloid malignancies, however, the prognostic role of SF3B1, U2AF1 or SRSF2 mutations in patients (pts) undergoing high intensity chemotherapy (HIC) and HCT has yet to be investigated. We evaluated 404 pts with the diagnosis of AML (n=96), MDS and MDS/MPN (n=294), MPN (n=13), and congenital sideroblastic anemia (n=1). 35 pts received HIC defined as treatment with 7+3, high dose cytarabine, clofarabine, or other comparable chemotherapy in the context of a clinical trial. 97 pts underwent a myeloablative (n=69) or reduced intensity (n=28) allogeneic HCT from an HLA matched related (n=39), unrelated (n=50) or cord blood (n=8) donor from April 2003 until August 2011. Median age of the whole cohort was 69 and those who underwent BMT at time of transplant was 52 (range 19–70). We performed direct sequencing for the three most commonly mutated spliceosome genes, SF3B1 (exon 13–16), SRSF2 (exon 1 and 2) and U2AF1 (exon 2–6). Given the close association between SF3B1 mutations and RS, we analyzed the impact of the presence or absence of RS on the outcomes associated with the type of therapy received. We found a total of 24 SF3B1 mutations in MDS and MDS/MPN (primarily in pts with RS), 37 SRSF2 mutations in MDS and MDS/MPN (primarily CMML), and 13 U2AF1 mutations in MDS, MDS/MPN and secondary AML. Among pts with MDS and MDS/MPN, significant overall survival (OS) differences were found between SF3B1 mutant and wild type (WT), (83 vs. 31 months, p=0.001) and U2AF1 or SRSF2 mutant (18 vs. 37 months, p=0.007). The U2AF1 mutation by itself was more strongly associated with poor outcome (8 vs. 37 months, p<0.0001), compared to an SRSF2 mutation (26 vs. 36 months, p=0.16). Analysis of survival according to treatment type revealed that no pts who underwent HIC or HCT carried an SF3B1 mutation. The presence of RS was also associated with improved survival (38 vs. 25 months, p=0.04), and this benefit remained if pts received HIC (18 vs. 9 months, p=0.04). However, this benefit became non-significant if pts underwent HCT. There were 19 pts who had either an U2AF1 or SRSF2 mutation that underwent HIC. Although it appeared that having either mutation was associated with worse survival, (9 vs. 21 months), it did not reach statistical significance (p=0.46). Among pts who underwent HCT, there were 10 pts who carried either an U2AF1 or SRSF2 mutation. Those pts with mutations appeared to have superior survival with HCT compared to WT, (53 vs. 34 months), but this did not reach statistical significance (p=0.54). Among pts with either an U2AF1 or SRSF2 mutation, those who underwent HCT had a superior survival (53 vs. 17 months, p=0.05) compared to those who received conventional chemotherapy, defined as HIC or low intensity chemotherapy (LIC), such as hypomethylating agents. There was no difference in survival between receiving HCT or conventional chemotherapy in pts who were WT for U2AF1 or SRSF2 (34 vs. 31 months, p=0.08). Consistent with previous findings of improved survival and loss of SF3B1 with leukemic progression in MDS and MDS/MPN pts, we found no SF3B1 mutations in our cohort of pts receiving HIC or HCT. In contrast, we found poorer outcomes with SRSF2 or U2AF1 mutations. Although the incidence of these mutations was rare in our cohort of pts, we found statistically significant survival benefit for pts with these mutations if they underwent HCT compared to conventional chemotherapy. This is the first study evaluating the impact of spliceosomal mutations on the survival outcomes of pts undergoing HCT. Our preliminary findings of improved survival with HCT in poorer-risk spliceosome mutations is provoking and further molecular analysis is ongoing. Disclosures: Maciejewski: NIH: Research Funding; Aplastic Anemia&MDS International Foundation: Research Funding.

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