scholarly journals 301: The Impact of the Disparities of Short Tandem Repeats (STR) between Doonor-recipient Pair on the Allogeneic Hematopoietic Cell Transplantation (AHCT) Outcome

2008 ◽  
Vol 14 (2) ◽  
pp. 111-112
Author(s):  
E. Serbest ◽  
P. Topcuoglu ◽  
K. Dalva ◽  
A.U. Bilgin ◽  
E.A. Soydan ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
The Impact ◽  
Short Tandem

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.

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