Pre-Transplant Risk-Assessment for Patients with Acute Myeloid Leukemia (AML) Receiving Allogeneic Hematopoietic Stem Cell Transplants.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2302-2302
Author(s):  
Philipp G. Hemmati ◽  
Theis H. Terwey ◽  
Philipp le Coutre ◽  
Gero Massenkeil ◽  
Lam G Vuong ◽  
...  

Abstract Abstract 2302 Poster Board II-279 Purpose: The presence of comorbidities was shown to have a substantial impact of the outcome of patients undergoing cancer treatment. In chronic myeloid leukemia (CML) the EBMT risk score proofed to be highly valuable in predicting the outcome of patients following allogeneic stem cell transplantation (alloSCT). We therefore investigated, whether a slightly modified EBMT risk score may be used to predict the outcome of patients with AML following alloSCT. Patients and Methods: We retrospectively analyzed 233 patients with AML (median age: 47 years, range: 17 – 68 years) who underwent alloSCT at our institution between 1994 and 2007. 180 patients (77%) had de novo AML and 53 patients (23%) had secondary or therapy-related AML. A favorable karyotype was present in 11 patients (5%) whereas 101 (43%) or 82 patients (35%) had an intermediate risk or a poor risk karyotype. 131 patients (56%) received myeloablative conditioning (MAC) whereas 102 patients (44%) were conditioned using reduced intensity conditioning (RIC). The EBMT risk score was calculated analogous to the original score established by Gratwohl et al. (Lancet 352, 1998) and included the following variables: age (<20, 20-40 or >40 years), interval from diagnosis to alloSCT (<1 year or ≥1 year), disease stage (CR1, >CR1 or no CR), donor/recipient gender match (female donor/male recipient or other), and donor type (HLA-identical sibling or other). Altogether, 6 patients (3%) were younger than 20 years, 82 patients (35%) were between 20-40 years, and 145 patients (62%) were older than 40 years. The interval from diagnosis to alloSCT was <1 year in 180 patients (77%) and ≥1 year in 53 patients (23%). 121 patients (52%) were transplanted in CR1, 41 patients (18%) underwent alloSCT >CR1, and 71 patients (30%) had active (relapsed/refractory) disease at the time of alloSCT. A female donor/male recipient transplantation was performed in 59 patients (25%). Transplants were from a matched-related donor (MRD) in 103 patients (44%). A matched-unrelated or a mismatched-unrelated donor was chosen in 101 (44%) or in 28 patients (12%). Only 1 patient was transplanted from a haplo-identical donor. Results: After a median follow-up of 48 months (range: 6 – 170 months) for the surviving patients, 108 patients (46%) are alive, 101 (43%) of which are in continuous CR. Causes of death (total 125 patients (54%)) were relapse in 70 patients (30%), infections/graft versus host-disease in 54 patients (23%), or other (1 patient (0.5%)). At 10 years after alloSCT, projected overall survival (OS) or disease-free survival (DFS) were 41% or 39%. Non-relapse mortality (NRM) or incidence of relapse were 32% or 43%. Of the 233 patients, 30 (13%) had an EBMT risk score of 0-1, 48 (21%) had a score of 2, 50 (21%) had a score of 3, 40 (17%) had a score of 4, 51 (22%) had a score of 5, and 14 (6%) had a score of 6-7. OS in the different score groups were 67% (score 0-1), 50% (score 2), 48% (score 3), 33% (score 4), 23% (score 5), or 21% (score 6-7) and differed significantly between the groups (p=0.0005). NRM in patients with an EBMT risk score >4 as an abritary cut-off was significantly higher as compared to patients with a score ≤4 (53% versus 25%; p=0.009). Likewise, the incidence of relapse was significantly lower in patients with an EBMT risk score ≤3 as an abritary cut-off when compared those with a score >3 (31% versus 57%; p<0.0001). In univariate analysis, disease stage had a negative prognostic impact on OS (CR1: 54%, >CR1: 32%, no CR: 25%; p<0.0001). Likewise, OS in patients with a MRD was significantly higher as compared to patients with other donor types (MRD: 50%, other: 34%; p= 0.003). In contrast, age, interval from transplantation to alloSCT, and donor/recipient gender match did not influence OS in our analysis. Conclusions: These data indicate that a modified EBMT risk score may be used to predict the outcome of patients with AML following alloSCT. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 1220-1226 ◽  
Author(s):  
Bronwen E. Shaw ◽  
Steven G.E. Marsh ◽  
Neema P. Mayor ◽  
Nigel H. Russell ◽  
J. Alejandro Madrigal

AbstractStudies in unrelated donor (UD) hematopoietic stem cell transplantations (HSCT) show an effect of the matching status of HLA-DPB1 on complications. We analyzed 423 UD-HSCT pairs. Most protocols included T-cell depletion (TCD). All pairs had high-resolution tissue typing performed for 6 HLA loci. Two hundred eighty-two pairs were matched at 10 of 10 alleles (29% were DPB1 matched). In 141 HLA-mismatched pairs, 28% were matched for DPB1. In the 10 of 10 matched pairs (n = 282), the 3-year probability of relapse was 61%. This was significantly higher in DPB1-matched pairs (74%) as compared with DPB1-mismatched pairs (56%) (log rank, P = .001). This finding persisted in multivariate analysis. In the group overall (n = 423), relapse was also significantly increased if DPB1 was matched (log rank; P < .001). These results were similar in chronic myeloid leukemia (CML; P < .001) and acute lymphoblastic leukemia (ALL; P = .013). In ALL, DPB1-matched pairs had a significantly worse overall survival (log rank; P = .025). Thus, in recipients of TCD UD-HSCT, a match for DPB1 is associated with a significantly increased risk of disease relapse, irrespective of the matching status for the other HLA molecules. It is possible that this effect is especially apparent following TCD transplantations and invites speculation about the function of DPB1 within the immune system.


2012 ◽  
Vol 2012 ◽  
pp. 1-5
Author(s):  
Sylwia Mizia ◽  
Dorota Dera-Joachimiak ◽  
Malgorzata Polak ◽  
Katarzyna Koscinska ◽  
Mariola Sedzimirska ◽  
...  

Eighty-six patients suffering from hematological malignancies, immunodeficiencies, and aplastic anemias received alloHSCT from unrelated donors. Donors were selected from the BMDW files and further matching was performed according to the confirmatory typing procedure with the use of PCR SSP and that based on sequencing. The time from the clinical request of the donor search to the final decision of clinicians accepting the donor was from 0.3 to 17.8 months (median 1.6). Matching was analyzed at the allele level, and 50, 27, and 9 donor-recipient pairs were 10/10 matched, mismatched in one or more alleles, respectively. In an univariate analysis we found better survival if patients were transplanted: (i) from donors matched 10/10 (P=0.025), (ii) not from female donor to male recipient (P=0.037), (iii) in female donation from those with ≤1 pregnancy than multiparous (P=0.075). Notably, it became apparent that duration of the confirmatory typing process affected the survival (HR = 1.138, P=0.013). In multivariate analysis only the level of matching and the duration of the matching procedure significantly affected the survival. In conclusion, the duration of the matching procedure in addition to the level of matching should be considered as an independent risk factor of survival.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2948-2948
Author(s):  
Jerzy Holowiecki ◽  
Sebastian Giebel ◽  
Jerzy Wojnar ◽  
Miroslaw Markiewicz ◽  
Aleksandra Holowiecka-Goral ◽  
...  

Abstract Unrelated donor - hematopoietic stem cell transplantation (URD-HSCT) is the treatment of proved long-term efficacy for chronic myeloid leukemia (CML) patients not having an HLA-identical sibling. However, high procedure-related toxicity observed after oral busulfan- or TBI-based conditioning limits its applicability and deteriorates outcome [Radich, Blood2003, 102, 31–5]. This is of increasing importance in the presence of challanging options offered by tyrosine kinase inhibitors. Between 2003–2006 we introduced a new preparetive regimen consisting of Treosulfan (a soluble alkylyting agent) 14 g/m2/d on days -6, -5, -4, Fludarabine 30 mg/m2/d on days -6, -5, -4, -3, -2, and, anti-thymocyte globulin (ATG) at a total dose of 6 mg/kg. Thirty patients (age 32, range 16–48 years) with CML in the 1st chronic phase (n=29) or in 2nd chronic phase (n=1) were included in the study. Median interval from diagnosis to alloHSCT equaled 1.0 (0.5–12.0) years. 63% of patients had previously been treated with Imatinib. The donors were selected based on high resolution typing for both HLA class I and II. 43% of donors were mismatched for a single HLA-C (n=9), HLA-DQB1 (n=3) or HLA-B locus (n=1). Bone marrow was used a source of stem cells in 19 patients, peripheral blood - in 11 cases. GVHD prophylaxis consisted of Cyclosporin A and short-course Methotrexate. All patients engrafted with the median time to neutrophil recovery >0.5 G/L and PLT >50 G/L of 19 (10–30) days and 18 (12–29) days, respectively. Complete donor chimerism was achieved until day +100 in all but one patient. Grade 3–4 neutropenic infections occurred in 13% of patients. Grade 3–4 mucositis as well as hepatic toxicity including VOD were not observed. The incidence of grade II acute GVHD was 23%, whereas grade III-IV acute GVHD was not observed. The incidence of extensive chronic GVHD was 10%. At 3 years the probability of the overall survival and hematological relapse-free survival equaled 82% (+/−7%). The cumulative incidence of non-relapse moratlity was 18% (+/−7%) (fungal infection n=3, bacterial infection n=1, EBV-LPD n=1). Four patients required donor lymphocyte infusion or additional interferon or imatinib treatment because of incomplete donor chimerism or molecular/cytogenetic relapse after initial response. We conclude that treosulfan + fludarabine + ATG conditioning is associated with low organ toxicity, low incidence of severe GVHD and NRM. The regimen is feasible option for CML patients referred for URD-HSCT in tyrosine kinase inhibitors era.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5258-5258
Author(s):  
Veronica Ortiz Corbella ◽  
Quoc-Hung Lê ◽  
Franck E. Nicolini ◽  
Anne Thiébaut ◽  
Xavier Thomas ◽  
...  

Abstract RIC regimens followed by allogeneic hematopoietic stem cell transplantation (HSCT) were evaluated in patients with hematologic malignancies who were not candidates for conventional transplantation because of age or medical co-morbidities. In this kind of transplantation, the analysis of chimerism kinetics remains fundamental. The main aims of this study were to evaluate and compare the impact of pre- and post-transplant variables and chimerism on transplantation outcome. Chimerism status was evaluated in total blood (TB) and in purified CD3+ cells using quantitative PCR (STR/SNP) for all. We analysed donor type and kinetics chimerism of 52 patients (32 M - 20 F) who had undergone allogeneic HSCT after RIC for hematological malignancies. Median age was 40 years (range 25–67 years). Diagnosis were multiple myeloma: 16, acute myeloid leukemia: 13, myelodysplasia: 6, chronic lymphocytic leukemia: 5, Non Hodgkin’s lymphoma: 5, acute lymphoblastic leukemia: 1, chronic myeloid leukemia: 2 and primitive myelofibrosis: 4. Conditioning regimens were Fludarabine + Busulfan in 33 patients, Fludarabine + 2 Gys total body irradiation 15, Cyclophasphamide 3 (2 alone/one with Busulfan) and one other chemotherapy. Stem cell source was PB in all except one who received cord blood. Fourty-eight were identical sibling and 4 unrelated donor transplantations. At transplant, 17 patients were in CR, 21 PR and 14 in evolutive diseases. All patients except one engrafted. Twenty-five developed aGVHD ≥ Grade II (16 Grade III-IV). At the last follow-up 22 patients died (9 disease progression and 13 of transplant related mortality, 30 were alive (18 developed chronic graft vs Host disease (cGVHD) 12 extensive/6 limited cGHVD). Among 52 patients, only 49 had a long-term chimerism documentation of CD3 subpopulation (43 TB and CD3+ cells): 15 (14 TB) were full donor chimerism (FDC) throughout the follow-up, and 34 remained mixed chimerism (MC). Among these 34 (29 TB) MC patients at the latest follow-up, 7 (5 TB) remained in MC, 2 (5 TB) converted to recipient profile and 25 (19 TB) converted to donor profile. Univariate analysis demonstrated the close correlation between chimerism status evaluated on PB CD3+ cells only at any time post-transplant and the onset of aGVHD (p = 0.0391) but not cGVHD. Multivariate analysis according to linear regression method did not find any impact of the following variables on chimerism kinetics after RIC transplant: disease status before transplant, age, sex, type of RIC regimen, number of days of ATG, aGVHD (p ≥ 0.11). In conclusion, this study underlines the tight correlation that exists between chimerism status and kinetics on CD3+ PB subpopulations after RIC transplant and acute GVHD development that impacts on transplant outcome.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1922-1922
Author(s):  
Takuya Yamashita ◽  
Takahiro Fukuda ◽  
Shuichi Taniguchi ◽  
Kazuteru Ohashi ◽  
Saiko Kurosawa ◽  
...  

Abstract Abstract 1922 In allogeneic hematopoietic stem cell transplantation (HSCT) for recipients with acute myeloid leukemia (AML), cyclophosphamide (Cy) combined with total body irradiation (TBI) (Cy+TBI) is the most common myeloablative conditioning (MAC) regimen, but busulfan (Bu) in combination with Cy (Bu+Cy) has been an alternative to Cy+TBI since early 1980s. But as oral Bu has a problem of interpatient variation in intestinal absorption, intravenous Bu (ivBu) has been developed and substituted for Bu in conditioning regimens for HSCT. For the last decade, fludarabine (Flu)-based regimens with the addition of cytotoxic agents such as Bu or melphalan (L-PAM) have been developed as reduced-intensity conditioning (RIC) regimens. After the introduction of ivBu, Flu+ivBu has become one of the common RIC regimens. In Japan, ivBu was introduced in 2006 and have been widely used as a part of conditioning regimens. In this nationwide retrospective study, we evaluated the clinical outcomes of allogeneic HSCT for AML, especially focusing on ivBu-based conditioning regimens. The study population included HSCT recipients reported to the Japan Society for Hematopoietic Cell Transplantation. From this database, we extracted the data of adult patients with AML who received first allogeneic HSCT between 1975 and 2010. There were 9,396 recipients selected according to this criterion. Then, we excluded 345 (3.7%) cases from the study because of missing key variables. A total of 9,051 recipients were evaluated in this study. Median age at transplant was 43 years (range, 16–82), and 41.8% (n=3,785) were female. Types of transplant included bone marrow transplantation from sibling donor (RBMT) (n=1,978, 21.9%), peripheral blood stem cell transplantation from sibling donor (RPBSCT) (n=1,411, 15.6%), bone marrow transplantation from unrelated donor (UBMT) (n=3,321, 36.7%) and cord blood transplantation from unrelated donor (CBT) (n=1,728, 19.1%). MAC regimens were applied to 80.2% (n=7,259) of recipients and RIC regimens to 19.8% (n=1,792), according to the definitions proposed by the NMDP and the CIBMTR in 2007. These MAC regimens included Bu+Cy-based (12.4% of all MAC regimens), Cy+TBI-based (50.0%) and ivBu+Cy-based (5.6%) regimens. RIC regimens consisted mainly of Flu+Bu-based (27.6% of all RIC regimens), Flu+L-PAM-based (24.1%) and Flu+ivBu-based (19.5%) regimens. Median follow-up of survivors was 1,437 days (range, 26–8,344). In MAC setting, overall survival (OS) of HSCT recipients with ivBu+Cy-based regimens did not show the significant difference between that with Bu+Cy or Cy+TBI-based ones in RBMT (p=0.168), RPBSCT (p=0.236) and UBMT (p=0.604). But in CBT, Cy+TBI was significantly superior to Bu+Cy (p=0.004). Though the cumulative incidences of relapse (RI) were similar among recipients with these three regimens, the cumulative incidence of non-relapse mortality (NRM) with Bu+Cy was significantly higher than with Cy+TBI in CBT (p=0.049). In RIC setting, OS of recipients with Flu+ivBu-based regimens was comparable to that with Flu+Bu or Flu+L-PAM-based ones regardless of the type of transplant. RIs with these three regimens were almost equivalent, but NRM with Flu+ivBu-based was significantly lower than that with Flu+L-PAM-based in UBMT (p=0.023). In the multivariate analysis for OS, ivBu+Cy-based regimens did not have significant impacts regardless of the type of transplant, but Flu+ivBu-based regimen had a significantly favorable impact in RBMT (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.23–0.99). In the multivariate analysis for NRM, Flu+ivBu-based regimen had a significantly reduced risk compared with Flu+L-PAM in RBMT (HR 0.32, 95%CI 0.11–0.95) and UBMT (HR 0.46, 95%CI 0.25–0.83). These data indicates that ivBu+Cy-based and Cy+TBI-based MAC regimens have almost equivalent efficacy profiles for OS, RI and NRM, and Flu+ivBu-based RIC regimens can reduce the risk of NRM compared with Flu+Bu and Flu+L-PAM-based ones in allogeneic HSCT for recipients with AML. Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 70 (suppl. 1) ◽  
pp. 63-65
Author(s):  
Marija Elez ◽  
Lavinika Atanaskovic ◽  
Svetlana Mirosavljevic ◽  
Gordana Ostojic ◽  
Biljana Todoric-Zivanovic ◽  
...  

Introduction. Allogeneic stem-cell transplantation is only potentially curative therapy for variety of hematology malignancies, such as acute and chronic leukemia, myelodisplastic syndrome and aplastic anemia, but also promising treatment option for other disorders. If we know that only 25% of patients have an human leukocyte antigen identical sibling donor, it is obvious that matched unrelated donor hematopoietic stem cell transplantation is an alternative for the rest of the patients. Material and Methods. Since 2013, matched unrelated donor hematopoietic stem cell transplantation has been performed routinely in the Military Medical Academy. Results. We hereby present the outcome after 77 procedures in 75 patients. Considering primary diseases, 35 patients had acute myeloid leukemia, 25 patients had acute lymphoid leukemia, 5 patients had chronic myeloid leukemia, 9 patients had myelodisplastic syndrome and we performed the transplant on 1 patient with chronic lymphocyte leukemia, 1 patient with aplastic anemia and 1 patient with T lymphoblastic lymphoma. Conclusion. It is difficult to make clear conclusions based on this heterogeneous group of patients, but it seems that these results are encouraging. Future research will be performed to evaluate matched unrelated donor and identical sibling hematopoietic stem cell transplantation in the homogenous groups with respect to primary diseases.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4480-4480
Author(s):  
Monica Magdalena Rivera Franco ◽  
Eucario Leon Rodriguez

Background: Our institutional HSCT Program was formally established in 1986, performing 33 transplantations throughout the following decade, obtaining an overall survival (OS) of 28% and a high non-relapse mortality (NRM) (61%) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). According to these unfavorable results, in 1998 our program was restructured with the consequent development of a modified HSCT method (reduced BuCy 2) adapting to our limited resources with the objective of decreasing the NRM and improving the OS. Objective: To describe the outcomes of allo-HSCT using reduced BuCy 2 as conditioning regimen in a Mexican referral center. Patients and Methods: A retrospective study was performed including consecutive patients undergoing allo-HSCT at the National Institute of Medical Sciences and Nutrition Salvador Zubiran, from May 1999 to May 2019. Data was obtained from a prospectively created database. Reduced BuCy 2 consisted of busulfan 12 mg/kg, ORAL and cyclophosphamide 80mg/kg, IV. Therapeutic busulfan monitoring was not available. Cyclosporine A (CsA) and methotrexate (MTX) were given for GVHD prophylaxis. Blood products, nutritional support, and antimicrobial prophylaxis were provided according to institutional guidelines. Disease risk index (DRI) was classified as low, intermediate or high using standard definitions and the HCT-CI score was assigned to each patient. Morbidity post-transplant was analyzed through the toxicity evaluation according to the NCI CTCAE v4.0, which classifies each toxicity as grades I-IV. Veno-occlusive disease (VOD) was diagnosed according to the modified Seattle criteria. Graft-versus-host disease (GVHD) was evaluated according to NIH guidelines. Endpoints included OS and NRM. Descriptive statistics were used. Kaplan-Meier curves were used to analyze survival using SPSS v.21. Results: Ninety-four patients were included. Table 1 shows patient and HSCT characteristics. Most were males (54%) and the median age was 31.5 years. The most common diagnosis was acute lymphoblastic leukemia (ALL) (33%), followed by myelodysplastic syndrome (MDS) (22%), and Chronic myeloid leukemia (CML) (16%). Most patients had an intermediate DRI (55%) and the HCT-CI score was mostly low (72%). Only 6% of allo-HSCT used a matched unrelated donor. The most frequent source of HSCs was G-CSF-primed bone marrow (56%). Toxicity to the chemotherapy regimen was observed in 89%, from which 48% were grades III-IV. VOD was observed in 2 patients. Most common infections included neutropenic fever (46%) and colorectal affection (12%). Invasive fungal disease was observed in 9% and CMV reactivation in 1%. Median days of engraftment were 15 and 20 for platelets and neutrophils, respectively. No engraftment failure was observed. Acute and chronic GVHD was observed in 26% (88% grades I-II) and 39% (86% limited disease), respectively. Thirty and 100-day NRM was 1% and 7%, respectively. Ten-year OS was 54% for all the cohort and the most frequent cause of death was relapse (61%) followed by GVHD (26%), and infections (13%); by disease, it was as follows: ALL 30%, acute myeloid leukemia 57%, CML 64%, lymphomas 33%, MDS 85%, and others 50%. Conclusion: Reduction in NRM has been of interest in allo-HSCT over the years, requiring more effective strategies. Since 1998, we have used an adjusted conditioning method for allo-HSCT due to the high toxicity and mortality related to conventional BuCy2 at the beginning of our HSCT Program. Our regimen consists of reducing conventional BuCy2 (˂ 25% of Bu and ˂ 20% Cy), preserving its myeloablative potential, considering reduced tissue injury, and therefore, reduced systemic toxicity; consequently maintaining immunosuppression for fast engraftment, and reducing NRM. Mucositis was the main toxicity but it resolved with supportive care. Grade III-IV aGVHD was low (12%), as well as extensive cGVHD (14%). Thirty and 100-day NRM was very low. The findings of our study demonstrate that reduced BuCy2 regimen associates with minimal morbi-mortality and might represent an alternative for conditioning in the allo-HSCT context, especially in limited resource centers at developing countries were novel agents and total body irradiation are not available. Disclosures No relevant conflicts of interest to declare.


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