Reduced-intensity allogeneic hematopoietic stem cell transplantation combined with imatinib has comparable event-free survival and overall survival to long-term imatinib treatment in young patients with chronic myeloid leukemia

Abstract Abstract 4459 IL10 is a pivotal immunomodulatory cytokine and is usually regarded as a suppressor of the immune responses. However, IL10 has been shown to have some immunostimulatory effects. The IL10-592 CC genotype is associated wit higher production of IL10. Because IL10 may promote the development of alloimmunity we hypothesized that the IL10-592 CC genotype in the donor reduces the risk of relapse after hematopoietic stem cell transplantation (HSCT). A cohort of 211 children (median age, 12 years) with acute lymphoblastic leukemia (n=100), acute myeloid leukemia (n=62), myelodysplastic syndrome (n=30) or chronic myeloid leukemia (n=19) who underwent allogeneic bone marrow (n=153) or peripheral blood stem cell transplantation (n=58; T-cell depleted: n=26) in a single center and/or their respective donors was genotyped of IL10 gene for rs1800872 using TaqMan real-time polymerase chain reaction. The donor was HLA-matched unrelated in 48% of transplants and HLA-identical related in 42% of transplants. Conditioning regimen was myeloablative in all cases. Two forms of post-transplant immunosuppression predominated, cyclosporine A and methotrexate in 69% of transplants and cyclosporine A alone in 17% of transplants. Cell samples from the donor were available in 174 cases and from the patient in 197 cases. The IL10-592 CC genotype was present in 82 of the 174 donors (47.1%) and in 104 of the 197 patients (52.8%). Interestingly, we found a significantly reduced incidence of relapse in patients who were transplanted from a donor with the IL10-592 CC genotype (15.9% versus 30.4%; p=0.016). In addition, we observed a significant increase of event-free survival (52.4% versus 33.7%; p=0.019) and a significant increase of overall survival (54.9% versus 37.0%; p=0.040) if the IL10-592 CC genotype was present in the donor. The occurrence of the IL10-592 CC genotype, in either donors or recipients, had no significant impact on treatment related mortality, acute and chronic graft-versus host disease. In conclusion, IL10-592 CC genotype in the donor is associated with a significant decrease of relapse rate and a significant increase of event-free survival and overall survival after HSCT in children with hematological malignancies. This is the first study to describe an association of IL10 gene polymorphism with relapse rate after HSCT. Selecting a donor with the IL10-592 CC genotype could be a useful therapeutic strategy for improving the final outcome after allogeneic HSCT. Disclosures: No relevant conflicts of interest to declare.

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TKI Treatment Discontinuation: How Many Patients Could Stop Tyrosine Kinase Treatment According to Discontinuation Trials Criteria? Incidence and Prognostic Impact of Deep Molecular Response in a Cohort of Chronic Myeloid Leukemia Patients of South Brazil's Hematology Centers

Blood ◽

10.1182/blood.v124.21.5542.5542 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5542-5542

Author(s):

Laura Fogliatto ◽

Marcelo Eduardo Zanella Capra ◽

Mariza Shaan ◽

Tito Vanelli Costa ◽

Luis Carlos Zanandrea Contin ◽

...

Keyword(s):

Overall Survival ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Molecular Response ◽

Imatinib Treatment ◽

Event Free Survival ◽

Free Survival ◽

The Future ◽

Tki Discontinuation

Abstract Sustained deep molecular response (MR4.5) after imatinib treatment defines a subgroup of patients with chronic myeloid leukemia (CML) with better outcome and that probably would be able to stop treatment in the future, according to results of clinical TKI discontinuation trials. Most of these trials showed that patients with a long-term imatinib treatment and low Sokal risk have a higher probability of maintain a deep molecular remission after stopping treatment. OBJECTIVES The main objective is to review the molecular responses, overall survival and event free survival of CP CML patients that have been treated with imatinib in 14 hematology centers in South Brazil. Using our data basis we also would like to see how many of them present long-term imatinib treatment, sustained deep molecular remission and correlate these findings with the Sokal risk groups. These data would allow us to predict patient profile that could be able to discontinue the treatment in the future in a prospective clinical trial. PATIENTS AND METHODS This is a retrospective study in a cohort of pts with chronic myeloid leukemia chronic phase (CP) that have been treated in 14 hematology centers in South Brazil. All pts received imatinib 400mg as first or second-line therapy. Patient evaluation and response criteria followed the ELN recommendations. MR(4.5) was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction. All tests were performed at a central standardized according to ELN. Event-free-survival (EFS) was measured from the start of imatinib to the date of any of the following events while on therapy: death from any cause, loss of complete hematologic response, loss of complete cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, or progression to accelerated phase or blastic phase. Overall survival (OS) was measured from the start of imatinib until death of any cause or to the date patient was last known to be alive. RESULTS Data from 474 patients was analyzed. After a median observation time of 46 months, 5-year overall survival (OS) was 86%, 5-year event-free-survival was 53%. Of the 474 patients, 258 had adequate PCR evaluations during treatment. 118 of 258 (45,7%) patients achieved MR(4.5) and 69 of 258 (27%) had sustained response for at least two years after a minimum time of treatment of 3 years. The cumulative incidence of MR(4.5) after 9 years was 76% (median, 3 years). In the group that achieved MR(4.5), there was only 1 (0,8%) death and 1 (1,1%) progression compared to 8 deaths (5,7%) and 8 progressions (7,5%) in the group without MR(4.5); these differences were significant with p=0,03 and 0,02 respectively. In the subgroup of 69 patients that had had been treated with imatinib for 3 year or more and sustained deep response (RM4,5) for at least two years, 21 pts had low Sokal risk, 7 pts intermediate Sokal risk and only 4 pts a high Sokal risk. Unfortunately, in 37 pts the Sokal risk could not be accessed due to missing information. CONCLUSION In our series MR(4.5) is reached in the majority of patients with long-term imatinib treatment. MR(4.5) is a predictor of outcome with only one disease progression and one death due to CML in this group of patients. Unfortunatly PCR are not available for all patients in our clinical practice, but this situation are improving. Regarding the 69 patients with TKI discontinuation trial criteria, we find out that 21 patients fulfill such criteria. In the future, according to the results of current stop trials it could be possible include this selected group of CP CML patients in a prospective clinical trial. Disclosures No relevant conflicts of interest to declare.

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Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis

Blood Advances ◽

10.1182/bloodadvances.2020001748 ◽

2020 ◽

Vol 4 (9) ◽

pp. 1998-2010 ◽

Cited By ~ 3

Author(s):

Matthias Felber ◽

Colin G. Steward ◽

Karim Kentouche ◽

Anders Fasth ◽

Robert F. Wynn ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

T Cell ◽

Hemophagocytic Lymphohistiocytosis ◽

Sinusoidal Obstruction Syndrome ◽

Event Free Survival ◽

Reduced Intensity Conditioning ◽

Hematopoietic Stem ◽

Free Survival ◽

Reduced Intensity

Abstract Reduced-intensity/reduced-toxicity conditioning and allogeneic T-cell replete hematopoietic stem cell transplantation are curative in patients with hemophagocytic lymphohistiocytosis (HLH). Unstable donor chimerism (DC) and relapses are clinical challenges . We examined the effect of a reduced-intensity conditioning regimen based on targeted busulfan to enhance myeloid DC in HLH. The European Society for Bone and Marrow Transplantation–approved reduced-intensity conditioning protocol comprised targeted submyeloablative IV busulfan, IV fludarabine, and serotherapy comprising IV alemtuzumab (0.5-0.8 mg/kg) for unrelated-donor and IV rabbit anti–T-cell globulin for related-donor transplants. We assessed toxicity, engraftment, graft-versus-host disease (GHVD), DC in blood cell subtypes, and overall survival/event-free survival. Twenty-five patients from 7 centers were treated (median age, 0.68 year). The median total dose and cumulative area under the curve of busulfan was 13.1 mg/kg (6.4-26.4) and 63.1 mg/L × h (48-77), respectively. Bone marrow, peripheral blood stem cell, or cord blood transplants from HLA-matched related (n = 7) or unrelated (n = 18) donors were administered. Donor cells engrafted in all patients (median: neutrophils d+20/platelets d+28). At last follow-up (median, 36 months; range, 8-111 months), the median DC of CD15+ neutrophils, CD3+ T cells, and CD16+56+ natural killer cells was 99.5% (10-100), 97% (30-100), and 97.5% (30-100), respectively. Eight patients (32%) developed sinusoidal obstruction syndrome, resolving after defibrotide treatment. The 3-year overall survival and event-free survival rates were both 100%. None of the patients developed acute grade III to IV GHVD. Limited chronic GVHD was encountered in 4%. This regimen achieves excellent results with stable DC in patients with HLH.

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Imatinib Combined with Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation Versus Imatinib Alone for Young Patients with Chronic Myeloid Leukemia in Chronic Phase

Blood ◽

10.1182/blood.v124.21.4568.4568 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4568-4568

Author(s):

Yanmin Zhao ◽

Yi Luo ◽

Yamin Tan ◽

Jimin Shi ◽

Zhen Cai ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Stem Cell ◽

Myeloid Leukemia ◽

Young Patients ◽

Chronic Phase ◽

Risk Scores ◽

Hematopoietic Stem ◽

Matched Donor ◽

Reduced Intensity

Abstract Background and Aims The relative merits of reduced intensity hematopoietic stem cell transplantation (RIST) for chronic myeloid leukemia (CML) in the first chronic phase (CP) in the imatinib (IM) era have not previously been evaluated. This prospective clinical trial was designed to compare the medical outcomes, with combination therapy of RIST plus imatinib versus imatinib alone in treating young patients with first CP including the early CP (ECP; a CML duration < 12 months) and the late CP (LCP; a CML duration ∼12 months). Patients and methods From January 2005 to January 2013, Patients aged ¡Ü 49 years, who were treated consecutively at the First Affiliated Hospital of Zhejiang University, were non-randomly assigned to treatment with imatinib alone or RIST group according to whether the patient had an HLA-matched donor; those with an HLA-matched donor were assigned to the RIST group, and the others were assigned to the imatinib group. In the RIST group, the conditioning regimen was based on busulfan, fludarabine and anti-thymocyte globulin, combined with pre-transplant imatinib for 3-12 months and post-transplant imatinib for 12 months. Results In total, 130 patients with the age from 11 to 49 years old were recruited, 42 patients were assigned to the RIST group and 88 patients were assigned to the imatinib group, respectively. Based on an eight-year follow-up period, the overall survival (OS) and event-free survival (EFS) were comparable between RIST and IM group (8 year-OS: 85.5% vs 89.0%, p=0.186; 8 year-EFS: 78.2% vs 73.9%, p=0.59). Interval from diagnosis to imatinib treatment more than 12 months (Late CP), high socal score, and no complete cytogenetic response at 3 month to IM were the adverse prognostic factors for EFS and OS, but only the time from diagnosis to imatinib was an independent predictor after multivariate analysis (OS: estimated HR=5.8, P=0.009; PFS:estimated HR=4.7, P=0.01). Among the ECP patients, imatinib alone was superior to RIST, with 8-year EFS rates of 92.3% vs 83.4% (p=0.05) and OS rates of 96.6% vs. 90% (P=0.03), respectively. Among LCP patients, both treatments resulted in similar survival (8-year OS rate: 62.6% vs 64.8%, p=0.53), but more LCP patients in the imatinib alone group experienced events as defined for 8-year EFS rate of 25.6%, compared with those in RIST group, with 8-year EFS rate of 48% P=0.047). The outcome of RIST was also released in the study. Primary graft failure occurred in two patients. Eleven (26.2%) developed grade I–II aGVHD, and one (2.4%) developed grade III–IV aGVHD. cGVHD could be evaluated in 39 patients, of whom 13 (33.3%) developed limited cGVHD and only 4 (10.2%) developed extensive cGVHD. The 100-day treatment-related mortality (TRM), one-year TRM and 8-year TRM was 2.5%, 10% and 12.7%, respectively. The patients were treated with 12-month imatinib for relapse prophylaxis, and the 2-year relapse rate was 10.5%. There was no late relapse (relapse after two year post-transplantation ) case. The patients with higher EBMT risk scores (3-5) had an inferior survival than those with lower EBMT risk scores ( 69.2% vs 92.9%, P = 0.04), and the EBMT risk score was an independent risk factor for OS with an odds ratio of 5.1 in multivariate analysis. Conclusions We concluded that imatinib alone confers significant survival advantages for young patients with CML in the ECP. For those in the LCP, both treatment arms resulted in similar overall survival, but RIST plus IM group resulted superior EFS, compared with IM alone. Thus, imatinib is superior to transplantation as the first-line therapy for young patients in the ECP, as for LCP, RIST should be considered to combined with pre-transplant and post-transplant IM as the treatment choice, especially when the patient get low EBMT risk scores. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia

Blood ◽

10.1182/blood-2007-04-085969 ◽

2007 ◽

Vol 110 (9) ◽

pp. 3456-3462 ◽

Cited By ~ 38

Author(s):

Partow Kebriaei ◽

Michelle A. Detry ◽

Sergio Giralt ◽

Antonio Carrasco-Yalan ◽

Athanasios Anagnostopoulos ◽

...

Keyword(s):

Stem Cell ◽

Chronic Myeloid Leukemia ◽

Hematopoietic Stem Cell Transplantation ◽

Myeloid Leukemia ◽

Chronic Phase ◽

Reduced Intensity Conditioning ◽

Hematopoietic Stem ◽

Reduced Intensity

Abstract Allogeneic hematopoietic stem-cell transplantation (HSCT) remains an effective strategy for inducing durable remission in chronic myeloid leukemia (CML). Reduced-intensity conditioning (RIC) regimens extend HSCT to older patients and those with comorbidities who would otherwise not be suitable candidates for HSCT. The long-term efficacy of this approach is not established. We evaluated outcomes of 64 CML patients with advanced-phase disease (80% beyond first chronic phase), not eligible for myeloablative preparative regimens due to older age or comorbid conditions, who were treated with fludarabine-based RIC regimens. Donor type was matched related (n =30), 1 antigen-mismatched related (n =4), or matched unrelated (n =30). With median follow-up of 7 years, overall survival (OS) and progression-free survival (PFS) were 33% and 20%, respectively, at 5 years. Incidence of treatment-related mortality (TRM) was 33%, 39%, and 48% at 100 days, and 2 and 5 years after HSCT, respectively. In multivariate analysis, only disease stage at time of HSCT was significantly predictive for both OS and PFS. RIC HSCT provides adequate disease control in chronic-phase CML patients, but alternative treatment strategies need to be explored in patients with advanced disease. TRM rates are acceptable in this high-risk population but increase over time.

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Conditioning with 8 Gy Total Body Irradiation and Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia: Projected 4-Year Update.

Blood ◽

10.1182/blood.v108.11.3016.3016 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3016-3016

Author(s):

Matthias Stelljes ◽

Martin Bornhaeuser ◽

Matthias Kroger ◽

Joerg Beyer ◽

Maria C. Sauerland ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Myeloid Leukemia ◽

Dna Typing ◽

Relapse Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Unrelated Donors ◽

Total Body ◽

Acute Myeloid

Abstract Seventy-one patients with acute myeloid leukemia (AML), most of them (63/71) considered ineligible for conventional allogeneic hematopoietic stem cell transplantation (HSCT), were enrolled into a phase II study on reduced intensity myeloablative conditioning with fractionated 8 Gy total body irradiation (TBI) and fludarabine (120 mg/m2) (Blood. 2005 Nov 1;106(9):3314–21). Patients received mobilized peripheral blood stem cells (n=68) or bone marrow (n=3) from siblings (n=39) or unrelated donors (n=32). HLA-typing was performed for HLA-A, -B, -Cw (serological matching or intermediate resolution DNA typing), DRB1 and DQB1 (high resolution DNA typing). Three patients had unrelated donors with an allele mismatch in HLA DRB1 (2 with an additional mismatch in HLA Cw) and 7 patients were transplanted from unrelated donors with an antigen mismatch in HLA Cw. Thirty-six patients were transplanted in complete remission (CR) and 35 with untreated or refractory disease (non-CR). Median patient age was 51 years (range, 20–66). Sustained engraftment was attained in all evaluable patients. With a median follow-up of now 41.3 months (range, 20.4–70.4) in surviving patients, probabilities of overall survival for patients transplanted in CR and non-CR were 80% (95% CI, 66 to 94%) and 17% (95% CI, 5 – 29%) at 4 years, respectively. Relapse-free survival rates were 57% (95% CI, 39 – 75%) and 14% (95% CI, 2 – 26%). Of the 35 evaluable patients transplanted in CR, 10 patients suffered a relapse between days 68 and 868 after transplantation (cumulative incidence 29%). Five patients with late relapse (>1 year after transplantation) achieved a subsequent CR after conventional chemotherapy, blood stem cell boost and treatment with granulocyte-macrophage colony-stimulating factor, lasting 2000+, 1841+, 909+, 847+ and 480 days, respectively. Depending on donor type, relapse-free survival was similar in patients transplanted from unrelated or sibling donors. Overall survival in patients transplanted in complete remission from unrelated vs. sibling donors was 84% (95% CI, 73 – 95%) vs. 77% (95% CI, 68 – 86%). The cumulative incidence of non-relapse mortality (NRM) in CR patients was 11% at 4 years and beyond (3 patients deceased before day 100 and 1 patient 25 months after transplantation), but amounted to 37% at 4 years in non-CR patients. Nine of the 33 surviving patients (27%) have actually active chronic GvHD (5 limited and 4 extensive disease). This update confirms that allogeneic HSCT from related or unrelated donors with 8 Gy TBI/fludarabine conditioning is feasible with low NRM and preserved long-term antileukemic activity in AML patients in first or later CR.

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Acute Myeloid Leukemia Treatment Outcomes: First Report from Single Center Retrospective Study in Kazakhstan

10.21203/rs.3.rs-757253/v1 ◽

2021 ◽

Author(s):

Jamilya Saparbay ◽

Gulnara Kulkayeva ◽

Vadim Kemaykin ◽

Aset Kuttymuratov ◽

Zhanna Burlaka ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Good Prognosis ◽

Event Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Acute Myeloid

Abstract Acute myeloid leukemia (AML) is the most common hematological malignancy in adults. In the last decade, internationally approved AML treatment guidelines, including hematopoietic stem cell transplantation are widely used in Kazakhstan. The categorization of acute myeloid leukemia was done according to the French-American British classification. The prognosis of patients at the time of diagnosis was determined by cytogenetic tests following the guidelines of the European LeukemiaNet. The overall survival and event-free survival were analyzed using the Kaplan-Meier method, and hazard ratios were defined with Cox regression. Totally 398 patients with AML were treated in the National Research Oncology Center between 2010 and 2020. The mean age was 38.3 years. We have found the correlation between ethnicity, cytogenetic group, white blood cell count, and treatment approaches with overall and event-free survival. There was a significantly longer OS in a cytogenetic group with a good prognosis compared with intermediate and poor prognosis. The median survival time in the group with a good prognosis was 43 months, 23 months in the intermediate group (p=0.7), and 12 months in the poor prognosis group (p=0.016). There was a significantly longer OS for the group of patients who received hematopoietic stem cell transplantation (HSCT), 52 months versus 10 months in the group who received chemotherapy only, p-value < 0.0001. Prognostic factors, such as cytogenetic group, initial WBC count, and treatment approaches are significantly associated with patient survival. Our study data were consistent with previous reports.

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Haploidentical Stem Cell Transplantation after Myeloabaltive Conditioning Is a Valid and Safe Option for Young Patients with Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma: A Study Compared with HLA-Matched Transplant

Blood ◽

10.1182/blood.v128.22.5849.5849 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5849-5849

Author(s):

Haiwen Huang ◽

Xiaofang Xiao ◽

Jia Chen ◽

Zhengming Jin ◽

Xiaowen Tang ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Young Patients ◽

Progression Free Survival ◽

Hematopoietic Stem ◽

Free Survival

Abstract Purpose: The role of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) therapy for refractory or relapsed (R/R) aggressive non-Hodgkin lymphoma (NHL) patients was still unknown. In this study, we aimed to explore the clinical outcome of R/R aggressive NHL patients received haplo-HSCT treatment. Patients and Methods: 23 R/R aggressive NHL patients who had undergone haplo-HSCT in our center between February 2006 and October 2015 were retrospectively analyzed, and 25 R/R aggressive NHL patients who received HLA-matched HSCT at the same period were also involved in this study. All patients received myeloablative conditioning (MAC) regimen, and antithymocyte globulin, cyclosporine A, mycophenolate mofetil and short course of methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. 12 patients had experienced autologous HSCT prior to allo-HSCT. Results: The median age of the total 48 patients was 33 (16-58) years old, and there were 33 males and 15 females in the total cohorts. The diagonosis were as following: 16 (33%) diffuse large B cell lymphoma and 22 (46%) peripheral T cell lymphoma. There were no difference in sex, age at transplantation, histologic diagnosis, aaIPI score, previous ASCT and conditioning regime between HLA-matched HSCT and Haplo-hsct groups. 44 patients had achieved engrafment, and the median times to neutrophil and platelet recovery were 12 and 15 days, respectively. Incidences of grade 3-4 acute GVHD were 18.3% in haplo-HSCT group and 16.7% in HLA-matched HSCT groups(p=0.87), while 2 years cumulative incidences of chronic GVHD in these two groups were 43.5% and 36.7% (P=0.68). For 16 patients who had chemoresistant disease at transplantation in haplo-HSCT group, four patients achieved complete remission, and ten patients achieved partial remission, while the other two patients experienced disease progression at 21 days and 37 days, respectively. With a median follow-up of 25 months, 12 patients experienced disease recurrence or progression in haplo-HSCT. And four patients died of transplantation related mortality: infection (n=2); acute GVHD (n=1) and multi-organ failure (n=1). There were no differences in overall survival (OS) rate at 2 years (52.8% vs 57.0%, P=0.85) and 2 years progress free survival (PFS) rate (52.7% vs 56.9%, p=0.73) between the haplo-SCT and HLA-matched SCT groups. Multivariate analyses suggested that old age (>45 years)(p=0.02), primarychemorefractory (p=0.04)and occurrence of grade3-4 aGVHD (p=0.01) may contribute to poor prognosis. Conclusion: Haploidentical hematopoietic stem cell transplantation withmyeloablative conditioning regimenachieved satisfactory outcome with acceptable side-effects. This approachcan be a feasible and acceptabletherapy for young patients withR/R NHLwho have no access to a HLA-matched donor. Figure Comparison of outcomes after haplo-SCT and HLA-matched SCT. (a) Overall survival, (b) Progression-free survival, (c) Cumulative incidences of grade3-4 acute GVHD, (d) cumulative incidences of chronic GVHD, (e) cumulative incidences of relapse, (f) cumulative incidences of non-relapse mortality. Figure. Comparison of outcomes after haplo-SCT and HLA-matched SCT. (a) Overall survival, (b) Progression-free survival, (c) Cumulative incidences of grade3-4 acute GVHD, (d) cumulative incidences of chronic GVHD, (e) cumulative incidences of relapse, (f) cumulative incidences of non-relapse mortality. Disclosures No relevant conflicts of interest to declare.

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Prognostic Significance Of EVI1 expression In Acute Myeloid Leukemia Patients With Intermediate and Adverse Cytogenetic Risk Undergoing Allogeneic Hematopoietic Cell Transplantation With Reduced-Intensity Conditioning

Blood ◽

10.1182/blood.v122.21.3383.3383 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3383-3383 ◽

Cited By ~ 1

Author(s):

Marius Bill ◽

Madlen Jentzsch ◽

Thoralf Lange ◽

Laura Kloss ◽

Rainer Krahl ◽

...

Keyword(s):

Overall Survival ◽

Myeloid Leukemia ◽

Hematopoietic Cell Transplantation ◽

Multivariable Analysis ◽

Event Free Survival ◽

Reduced Intensity Conditioning ◽

Free Survival ◽

Expression Status ◽

Reduced Intensity ◽

Acute Myeloid

Abstract Allogeneic hematopoietic cell transplantation (HCT) represents a post-remission therapy offering potential cure for acute myeloid leukemia (AML) patients (pts). Reduced-Intensity Conditioning (RIC) is increasingly used in AML pts undergoing HCT ineligible for conventional conditioning. The ecotropic viral integration site 1 (EVI1) gene maps to chromosome 3q26 and encodes a transcription factor that has an important role during embryogenesis. EVI1 activation, e.g. through chromosome 3 translocations, is found in several human myeloid disorders. The presence of EVI1 expression has been described as a predictor of poor outcome in pts treated with standard cytarabine based chemotherapy. Whether the expression of EVI1 also associates with outcome in AML pts undergoing RIC-HCT, with a therapeutic approach mainly based on a graft-versus-leukemia effect, remains unknown. Here we tested the prognostic impact of EVI1 expression in RIC-HCT treated AML pts. We analyzed 57 AML pts (median age, 61 years [y]; range 27–74y) who received RIC (Fludarabin 30mg/m^2 at day-4 to -2 & 2Gy total body irradiation at day 0)-HCT at the University of Leipzig, with pretreatment bone marrow material available. Donors were human leucocyte antigen (HLA)-matched related (n=6, 10.5%) or HLA-matched (n=41; 72%) or mismatched (>= 1 antigen; n=10; 17.5%) unrelated. At HCT 82.4% (n=47) of the pts were in complete remission (CR). 28.6% (n=14) had acute graft-versus-host disease (GvHD; >= grade 2) and 80.5% (n=33) (31.7% (n=13) limited; 48.8% (n=20) extensive) chronic GvHD. Median follow-up was 7.0 y for pts alive. Medical research council (MRC) genetic classification was: intermediate (n=39; 73.5%) or adverse (n=14; 26.5%). The pts were also characterized for CEBPA and NPM1 mutations, as well as presence of an FLT3-ITD at diagnosis. EVI1 expression was measured with quantitative reverse transcription polymerase chain reaction and normalized to 18S. 71.9% (n=41) of our pts were EVI1 expressers. The presence of EVI1 expression did not significantly associate with any clinical or biological characteristics. Still, by trend EVI1 expression associated with an adverse karyotype (P=.08) and NPM1 mutations (P=.16). The presence of EVI1 expression significantly associated with shorter overall survival (OS; P=.04) and event-free survival (EFS; P=.03; Figure 1).Figure 1Overall Survival(A) and Event-free Survival (B) in RIC-HCT treated AML pts according to EVI1 expression statusFigure 1. Overall Survival(A) and Event-free Survival (B) in RIC-HCT treated AML pts according to EVI1 expression status In multivariable analysis in our set, none of the analyzed clinical or biological parameters were significantly associated with OS or EFS. However, in multivariable analysis cytogenetics (intermediate vs. adverse) associated with OS by trend (P=.12); while EVI1 expression status (P=.14), cytogenetics (intermediate vs adverse; P=.11) and remission status at the time point of RIC-HCT (CR vs all other; P=.10) associated with EFS by trend. In conclusion, the presence of EVI1 expression associated with worse outcome in RIC-HCT treated AML pts. Pretreatment EVI1 expression may refine the risk stratification for AML pts undergoing RIC-HCT. Disclosures: No relevant conflicts of interest to declare.

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