Neutrophil Recovery Time Research Articles

Transplant Outcomes in Beta-Thalassemia Major Patients Receiving Combined Granulocyte Colony-Stimulating Factor-Primed Bone Marrow and Cord Blood Graft Compared to Granulocyte Colony-Stimulating Factor-Primed Bone Marrow Alone

Background: Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for thalassemia major^TM. Graft rejection (GR) and graft-versus-host disease (GVHD) are the primary obstacles to a successful outcome. Methods: We conducted a retrospective study of HSCT in 29 children (median age at transplantation: 6 years) with Beta-thalassemia (β-TM) after the combined infusion of granulocyte colony-stimulating factor-primed bone marrow (G-BM) and cord blood (CB) from the human leukocyte antigen (HLA)-identical sibling donors. We also compared the outcomes of the co-transplanted children with those of children with β-TM who received G-BM alone from an HLA-identical sibling donor (n = 26). Results: Compared to the G-BM transplant (G-BMT) recipients, those who received a co-transplant had a lower incidence of grade ≥II acute (17.24 vs. 30.7%, p = 0.047) and limited chronic (0 vs.15.4%, p = 0.022) GVHD as well as a lower incidence of GR (0 vs. 7.7%, p = 0.132). Neutrophil recovery time was faster in the co-transplant group (18.5 vs. 21 days, p = 0.04). All the patients were monitored until December 31, 2016; the median follow-up time was 74 months<unterline>,</unterline> and the 5-year thalassemia-free survival rate was 89.7% in the co-transplant group and 84.6% in the G-BMT-alone group (p = 0.590). Conclusions: A combined CB and G-BM graft from an HLA-identical sibling donor is an effective treatment option for TM in children, with less acute and chronic GVHD.

Clinical Efficacy of Decitabine-Based Chemotherapy Regimens in the Treatment of Newly Diagnosed Elderly Patients with Acute Myeloid Leukemia

To investigate the safety and efficacy of decitabine combined with CAG regimen in the treat-ment of newly diagnosed elderly patients with acute myeloid leukemia(AML). Fourty-nine patients with newly diagnosed acute myeloid leukemia (except M3) who were admitted to our hospital were selected. All the patients were older than 50 years old, and allogeneic hematopoietic stem cell transplantation could not be performed for various reasons. Decitabine-based chemotherapy regimens were used during induction therapy including single decitabine therapy(DAC), decitabine combined with CAG regimen(DAC-CAG) and decitabine combined with HAAG regimen(DAC-HAAG). Most of patients continued to use the original treatment after complete remission, while others were given the standard "3+7" regimen chemotherapy. A total of 2-4 courses of treatment was conducted in the majority of patients. All of the 49 patients completed the induction therapy, in which 26 cases achieved complete remission(CR), 7 cases achieved partial remission(PR) and no response(NR) existed in 16 cases. The complete remission and the overall response rate(ORR) were 53% and 67% respectively. The overall response rate of DAC group, DAC-CAG group and DAC-HAAG group were 17%, 77% and 63% respectively. 14 patients were infected and 1 patients died of pulmonary infection during the induction therapy. The median number of suspended red blood cells and platelet infused were 9 units and 69 units respectively. Neutrophil recovery time was 15.1 days while the platelet recovery time was 20.1 days during the induction therapy. The mean follow-up time was 21 months. Overall survival(OS) was 75% at 6 months, 30% at 1 year, and 26% at 2 year, while disease-free survival(DFS) was 83% at 3 months, 54% at 1 year, and 47% at 2 year. The induction therapy could reach CR that was an independent prognostic factor, however, the initial white blood cell count, platelet count, age, chemotherapy regimen, prognostic stratification and whether complical by pnenmonia during chemotherapy were not independent prognostic factors. The induction efficacy of decitabine combined with chemotherapy is superior to that of decitabine alone. The outcome of induction chemotherapy is an independent prognostic factor, however, the high white blood cell count, poor karyotype, complications and AML with myelodysplasia-related changes do not affect long-term survival. DAC-CAG regimen is effective and have relatively few adverse reactions in AML. It is suitable for the patients who are ineligible for conventional chemotherapy.

Associations between neutrophil recovery time, infections and relapse in pediatric acute myeloid leukemia.

Children with acute myeloid leukemia (AML) treated similarly show different toxicity and leukemic responses. We investigated associations between neutrophil recovery time after the first induction course, infection and relapse in children treated according to NOPHO-AML 2004 and DB AML-01. Newly diagnosed patients with AML with bone marrow blast<5% between day 15 after the start of the treatment and the start of second induction course, and in complete remission after the second induction course were included (n=279). Neutrophil recovery time was defined as the time from the start of the course to the last day with absolute neutrophil count<0.5×109 /l. Linear and Cox regressions were used to investigate associations. Neutrophil recovery time after the first induction course was positively associated with neutrophil recovery time after the remaining courses, and longer neutrophil recovery time (≥25 days) was associated with increased risk of grade 3-4 infections (hazard ratio 1.4, 95% confidence interval [CI], 1.1-1.8). Longer neutrophil recovery time after the first induction (>30 days) was associated with the increased risk of relapse (5-year cumulative incidence: 48% vs. 42%, hazard ratio 1.7, 95% CI, 1.1-2.6) for cases not treated with hematopoietic stem cell transplantation in first complete remission. Longer neutrophil recovery time after the first induction course was associated with grade 3-4 infections and relapse. If confirmed, this knowledge could be incorporated into risk stratification strategies in pediatric AML.

Analysis of Hematopoietic Reconstitution in Auto-Peripheral Blood Hematopoietic Stem Cell Transplantation

To explore the factors which may have influences on hematopoietic reconstitution of the auto-peripheral blood stem cell transplantation(auto-PBHSCT). The successful rate, the time of hematopoietic reconstitution and implantation status at 28 days after transplantation of 177 patients received auto-PBSCT were retropectively analyzed, in order to explore the factors which may have influences on hematopoietic reconstitution. The median time of neutrophil recovery was 12 days (8-21 days), implantation rate was 98.9%, all patients' neutrophil were recovered in 28 days. The median time of platelet recovery was 17 days (7-420 days), implantation rate was 95.5%, the cumulative incidence of platelet recovery at day 28 was 80.8%. Univariate analysis showed that the CD34+ cell number and the use of TPO had effect on neutrophils recovery time; the disease kinds, conditioning regimen and the infused CD34+ cell number had influence on platelets recovery time. Multivariate analysis showed that the CD34+ cell number was the independent influencing factor of neutrophils reconstitution time; the disease kinds, the CD34+ cell number were the independent influencing factors of platelet reconstitution time. Disease kinds and the CD34+ cell number were the independent influencing factors of hematopoietic reconstitution status of 28 days after transplantation. In auto-PBHSCT patients, disease kinds, conditioning regimen, the infused CD34+ cell number and the use of TPO have been confirmed to be independent influencing factors on hematopoietic reconstitution.

Clozapine-Associated Agranulocytosis Treatment With Granulocyte Colony-Stimulating Factor/Granulocyte-Macrophage Colony-Stimulating Factor

Clozapine is associated with hematological abnormalities, notably neutropenia, which may progress to agranulocytosis. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used to reduce the frequency and duration of clozapine-associated neutropenia. This review aims to explore the use, efficacy, and tolerability of these cytokines in the treatment of clozapine-associated agranulocytosis. We conducted a systematic review of published interventional and observational studies, case series, and case reports where G-CSF/GM-CSF was used to treat clozapine-associated agranulocytosis. We identified 29 reports (40 patients). The median duration of neutrophil recovery time after stopping clozapine and starting cytokine treatment was 7 days (range, 2-13 days) for those with agranulocytosis (absolute neutrophil count < 0.5 × 10 cells/L). Ninety-four percent (n = 29) had no serious adverse reactions, and no deaths occurred. Our findings indicate that G-CSF/GM-CSF use is well tolerated and suggest that G-CSF can sometimes be safely used to reduce the duration of neutropenia associated with clozapine use. However, the interpretation of this outcome is difficult, given the likely publication bias for positive outcomes in case reports.

Disease-specific hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes.

Hematopoietic stem cell transplantation (HSCT) using an optimized conditioning regimen is essential for the long-term survival of patients with inherited bone marrow failure syndromes (IBMFS). We report HSCT in 24 children with Fanconi anemia (FA, n=12), Diamond-Blackfan anemia (DBA, n=7), and dyskeratosis congenita (DC, n=5) from a single HSCT center. The graft source was peripheral blood stem cells (n=19) or cord blood stem cells (n=5). FA and DC patients received reduced-intensity conditioning, while DBA patients had myeloablative conditioning. The median numbers of infused mononuclear cells and CD34+ cells were 14.20×108/kg and 4.3×106/kg, respectively. The median time for neutrophil and platelet recovery was 12 and 18days, respectively. Complete donor engraftment was achieved in 23 of 24 patients. There was one primary graft failure. During a median follow-up of 27.5months (range, 2-130months), the overall survival in all patients was 95.8%. The incidence of grade II-III acute graft versus host disease (GvHD) and chronic GvHD was 29.2% and 16.7%, respectively. We conclude that HSCT can be a curative option for patients with IBMFS. Modification of the conditioning regimen based on the type of disease may lead to encouraging long-term outcomes.

Clinical outcome of decitabine combined with CAG regimen for treatment of acute myeloid leukemia ineligible for conventional chemotherapy

Objective To investigate the safety and efficacy of decitabine combined with CAG regimen in treatment of acute myeloid leukemia (AML) ineligible for conventional chemotherapy. Methods The data of 20 cases with AML ineligible for conventional chemotherapy from January 2013 to May 2015 were retrospectively analyzed. Decitabine combined with CAG regimen was used during induction therapy. The primary induction regimen was used 26 times after remission, the standard 3+7 regimen were used 7 times, and intermediate-dose cytarabine were used 3 times. The total course of treatment included 2-8 cycles. Results All of the 20 patients completed the first cycle of induction therapy, including 11 cases of complete remission (CR), 5 cases of partial remission and no response in 4 cases, and the overall response rate (ORR) was 80% (16/20). ORR was 69.2% (9/13) and 100.0% (7/7) in high-risk group and middle-low risk group respectively. ORR was 60.0% (6/10) in AML evolving from MDS. 8 patients were infected during the induction therapy and the infection rate was 40.0% (8/20). 2 patients were died of pulmonary infection. The median number of suspended red blood cell and platelet infused were (9.1±5.7) U and (57.5±51.9) U respectively. Neutrophil recovery time was (8.7±5.6) days during induction therapy. All patients were followed up for at least 1 year, and 12 cases were dead. Overall survival rate was 85.0% at 3 months, 80.0% at 6 months, and 40.0% at 1 year. While in 12 CR patients relapse-free survival rate was 75.0% at 3 months, 75.0% at 6 months, and 65.6% at 1 year respectively. Conclusion Decitabine combined with CAG regimen with high remission rate and well tolerance, can be used as a first therapy for AML ineligible for conventional chemotherapy. Key words: Leukemia, myeloid, acute; Decitabine; Drug therapy, combination; CAG regimen; Induction therapy

Engraftment Syndrome: An Updated Review

Engraftment syndrome is a constellation of clinical manifestations that occur at the time of neutrophil recovery following hematopoietic stem cell transplantation. There are several risk factors, but the reports on some of them are rather conflicting. Additionally, not only the clinical manifestations but also the laboratory findings are nonspecific and may overlap with several conditions such as acute graft versus host disease, drug toxicity, radiation-induced damage and infectious disorders. Treatment of symptomatic and severe forms is similar to that of graft versus host disease. Hence, there is a need for: revision of the diagnostic criteria, establishment of scoring system to determine prognosis and to direct therapy as well as the addition new criteria to differentiate it from other similar conditions.

Impact of Chronic Graft-Versus-Host Disease on Long-Term Outcomes of Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Adults with High-Risk Acute Lymphoblastic Leukemia in First Remission

Background : The role of reduced-intensity conditioning allogeneic hematopoietic cell transplantation (RIC-HCT) in adult acute lymphoblastic leukemia (ALL) remains unclear because the interpretation of transplantation outcome is mainly limited by the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of the criteria used to select patients for RIC-HCT. Previously, we conducted a phase 2 trial of RIC-HCT in adults with high-risk ALL who were ineligible for myeloablative conditioning and showed the potential role of this strategy, especially in patients in first complete remission (CR1). Here, we report the long-term outcomes of RIC-HCT by analyzing 122 consecutive adults with high-risk ALL in CR1, particularly focusing on the prognostic relevance of chronic GVHD.Methods: During the period between 2000 and 2014, 122 patients in CR1 (median age, 52 years [range, 15-65 years]; 54 Ph-negative ALL and 68 Ph-positive ALL) were given an identical RIC regimen consisting of fludarabine (150 mg/m2 in total) and melphalan (140 mg/m2in total). The indications for RIC-HCT were advanced age (≥50 years; n=79; 64.8%) and comorbid conditions (n=43; 35.2%). Graft sources were peripheral blood stem cells (n=118; 66 matched sibling donor, 23 matched unrelated donor, 29 mismatched unrelated donor) and bone marrow (n=4; 1 matched sibling donor, 1 matched unrelated donor, 2 mismatched unrelated donor). The median time to transplantation was 155.5 days (range, 103-291 days). GVHD prophylaxis was attempted by administering calcineurin inhibitors (cyclosporine for sibling donor transplants, tacrolimus for unrelated donor transplants) plus methotrexate. Antithymocyte globulin was administered to the patients who received mismatched unrelated donor grafts. If residual leukemia was detected in the absence of GVHD at 3 months after transplantation, calcineurin inhibitors were rapidly discontinued.Results: The median time for neutrophil and platelet recovery was 12 days (range, 8-30 days) and 13 days (range, 5-60 days) after RIC-HCT. Sixty-two patients developed acute GVHD (53 grade II, 5 grade III, 4 grade IV). The cumulative incidence of acute GVHD at 1 year was 50.8% (42.6% for Ph-negative and 57.4% for Ph-positive, P=0.152). Except for 11 patients with early deaths within 100 days, 77 developed chronic GVHD (30 mild, 29 moderate, 18 severe), resulting in a 5-year cumulative incidence of 63.6% (69.1% for Ph-negative ALL and 58.8% for Ph-positive ALL, P=0.319). The median time to onset of chronic GVHD was 140 days (range, 37-843 days) after transplantation. Cytomegalovirus reactivation >10,000 copies/mL was observed in 40.2% (44.4% for Ph-negative ALL and 36.8% for Ph-positive ALL, P=0.447). After a median follow-up duration of 57.9 months (range, 17.7-206.8 months), the 5-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 27.5% (23.9% for Ph-negative ALL and 30.2% for Ph-positive ALL) and 19.0% (17.4% for Ph-negative ALL and 20.3% for Ph-positive ALL), respectively, and the 5-year disease-free survival (DFS) and overall survival (OS) rates were 53.5% (58.4% for Ph-negative ALL and 49.7% for Ph-positive ALL) and 59.8% (60.2% for Ph-negative ALL and 59.3% for Ph-positive ALL). In multivariate analysis, the presence of chronic GVHD lowered CIR (HR, 0.23; 95% CI, 0.10-0.48; P<0.001), but severe chronic GVHD increased NRM (HR, 8.76; 95% CI, 3.39-22.6; P<0.001). Thus, the presence of mild to moderate chronic GVHD was closely related to better outcomes in terms of DFS (HR, 0.45; 95% CI, 0.32-0.64; P<0.001) and OS (HR, 0.44; 95% CI, 0.30-0.64; P<0.001) in all patients as well as in both subgroups of patients. In Ph-positive ALL subgroup of patients, patients without achievement of major molecular response until the time of transplantation had also significantly higher CIR (HR, 7.42; 95% CI, 3.04-18.10; P<0.001) and poorer DFS (HR, 3.47; 95% CI, 1.48-8.14; P=0.004) and OS (HR, 2.58; 95% CI, 1.03-6.47; P=0.043).Conclusion: Our long-term follow-up data with a uniform treatment strategy suggest that RIC-HCT is a valid alternative choice for providing a long-term disease control for adult high-risk ALL patients in CR1. Minimal residual disease-based treatment strategies to reduce leukemia cell burden before HCT and to enhance the graft-versus-leukemia effect are needed in the future. DisclosuresKim:ILYANG: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Lee:Alexion Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Inverse PAR1 Activity of Hematopoietic Stem Cells and BM Stromal Cells Mediates G-CSF-Induced Mobilization By Regulation of Nitric Oxide Generation

Hematopoietic stem and progenitor cell (HSPC) egress from the bone marrow (BM) to the circulation is tightly regulated and is accelerated during stress conditions, a process utilized for BM harvest. Recently, we demonstrated that mouse long term repopulating hematopoietic stem cell (LT-HSC) BM retention and their rapid release to the blood circulation are governed by a switch in nitric oxide (NO) generation via distinct coagulation-related protease activated receptor 1 (PAR1) cascades (Gur-Cohen S. et al., NM, 2016).Herein we report that surface PAR1 expression can be exploited and serve as a positive predictive marker for the efficiency of human CD34+ HSPC mobilization among healthy donors in clinical G-CSF-induced mobilization for matched allogeneic transplantations. We found that PAR1 expression on circulating leukocytes before G-CSF administration was positively correlated with higher yields of mobilized leukocytes after stimulation (P<0.001). In addition, the percentage of PAR1-expressing CD34+ HSPCs in the blood and their absolute numbers before initiation of mobilization positively correlated with peripheral blood leukocyte counts (P<0.001) and yield of mobilized CD34+ HSPCs (P=0.002). Importantly, tracing the consequences of the follow-up BM transplantation, we found accelerated neutrophil recovery in patients transplanted with mobilized cells expressing higher surface PAR1 levels at baseline (P=0.074), shortening the time for neutrophil recovery (neutrophil count>0.5 x 109/L) from an average of 14.6 days to an average of 11 days post-transplant. In addition, a trend of accelerated platelet production was documented to be related with higher PAR1 expression by circulating leukocytes prior to G-CSF stimulation. Consequently, poor mobilizer donors were characterized by extremely low surface PAR1 expression on circulating CD34+ cells prior to G-CSF stimulations. Herein we present a case report of a thrombophilic donor carrying the MTHFR mutation, expressing exceedingly low PAR1 levels at baseline, with the outcome of inadequate numbers of mobilized CD34+ HSPC in the blood following G-CSF treatments.To further gain insight into the role played by PAR1 signaling in the regulation of G-CSF-induced HSPC mobilization, we used mice as a functional preclinical small animal model. We found that antagonizing PAR1 signaling attenuated both steady state release and G-CSF-induced HSPC mobilization. Furthermore, co-administration of G-CSF with PAR1 antagonist attenuated secretion of BM stromal CXCL12 and abrogated upregulation of surface CXCR4 and PAR1 expression by BM HSPCs, all leading to significantly reduced HSPC migration, differentiation and mobilization. In support, PAR1-/- mice failed to efficiently mobilize HSPCs in response to G-CSF compared to wild type counterparts. Enforced HSPC recruitment by G-CSF treatments dramatically accelerated PAR1-dependent NO production by eNOS, known to promote TACE-mediated EPCR shedding and rapid LT-HSC mobilization. Concomitantly, circulating steady state and G-CSF-mobilized stem cells lack surface EPCR expression. Intriguingly, while EPCR expression by primitive BM stem cells was transiently reduced after G-CSF treatments, antagonizing PAR1 signaling along with G-CSF stimuli blocked NO generation and synchronically expanded BM EPCR+ LT-HSC and their supportive stromal progenitor cells (MSPCs), as confirmed by increased repopulation in transplanted mice. Finally, we report an inverse PAR1 expression and regulation by BM HSPC and stromal MSPCs in mediating G-CSF-induced mobilization. G-CSF induced elevation of PAR1 expression on BM HSPCs, providing the driving force for their enhanced NO mediated migration, proliferation, differentiation and recruitment to the circulation. Contrary, the levels of PAR1 expression were reduced on MSPCs in response to G-CSF treatment, and following NO generation by eNOS activity and CXCL12 secretion, resulted in reduced mesenchymal differentiation leading to accumulated numbers of immature mesenchymal (CFU-F) and osteoblast (CFU-OB) progenitor cells.Taken together, our study identifies and highlights inverse PAR1 signaling and NO generation as essential regulator of G-CSF induced HSPC mobilization and MSPC development opening new avenues to advance therapeutics for enhancing clinical G-CSF induced stem cell mobilization and transplantation protocols. DisclosuresRuf:Iconic Therapeutics: Consultancy.

Low-Dose Decitabine Combined with Modified Bucy Is More Effective Conditioning Regimen for High-Risk Patients with Acute Myeloid Leukaemia/Myelodysplastic Syndrome

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment options to hematologic malignancies. However, majority of patients with refractory or resistant AML/MDS can not achieve remission before transplantation. It is necessary to design a safe and effective conditioning regimen to reduce tumour burden, improve remission rates, decrease transplantation-related mortality, and improve disease-free survival (DFS) in patients with advanced acute myloid leukemia(AML) and myelodysplastic syndrom(MDS). One of the promising drugs of epigenetics is decitabine (DAC), which has a significant effect on a variety of hematologic malignancies including MDS and advanced AML. Furthermore, decitabine can not only up-modulate the tumor-associated antigen express on surface of leukemia cells to increase graft-versus-leukemia (GVL) effect but also can reduce the incidence of graft-versus-host disease (GVHD) by increase the number of regulatory T Cells (Tregs).Objective: To investigate the security and efficacy of conditioning regimen containing low-dose decitabine combined with modified BUCY regimen for advanced AML/MDS patients, explore the role of immunomodulatory activity post transplantation and compared this regimen with conventional modified BUCY regimen.Methods: Between January 2012 and March 2015, a total of 156 patients were enrolled in this retrospective study. In which, there were 46 patients who received a conditioning regimen of low-dose DAC and a modified BUCY regimen(DAC group) followed by allo-HSCT, and the second cohort consisted of 110 who only received a conventional modified BUCY regimen(Con group). Comparing the baseline of two groups, there were no significant difference except there were more advanced stage patients in DAC group(63% vs 32.7%,p=0.007). A modified BUCY conditioning regimen include semustine (250 mg/m2/d) for 1 d(-10d), cytarabine (2 g/m2 q12 h) for 2 d (-9 d to -8 d), busulfan (0.8 mg/kg/6 h) for 3 d (-7 d to -5 d), and cyclophosphamide (1.8 g/m2/d) for 2 d (-4 d to -3 d). Meanwhile, patients in the DAC group received the DAC treatment for 3 to 4 d with a total of 100 mg/m2 before modified BUCY regimen.Results: In DAC group, all patients engrafted successfully, including 29/46(63%) non-remission (NR) patients. However, there were seven patients presented graft failure in Con group. The transplantation-related mortality (TRM) rate was significantly lower in DAC group(0% vs 13.6%, p=0.019). The median time of neutrophil recovery was 12(10-21)d vs 12(10-23)d, and platelet recovery was 13(10-35)d vs 14(9-40)d, respectively in DAC and Con group, and there were no significant differences. With the median follow-up of 277.5(39-985)d and 221(3-1237)d in two groups, the cumulative relapse rate(RR) was 38.2% vs 36.8% (p=0.951). The incidence rate of aGVHD was lower in DAC group(26.7% vs 46.8%, p=0.034), while there were no diference in the incidence rate of cGVHD(68.4% vs 70.7%, p=0.598). Compared with Con group, the estimated 2-year overall survival (2yr-OS) rate and 2 year disease-free survival (2yr-DFS) rate were both higher in DAC group(2yr-OS:45.6% vs 75.3%, p=0.007, Fig 1; 2yr-DFS:39.1% vs 51.5%, p=0.076). Furtheremore, for patients in advanced stage before transplant, the estimated 2yr-OS was 37.2% vs 72.7%(p=0.009) and 2yr-DFS rate was 38.5% vs 49.8%(p=0.051), respectively. For AMLs, the estimated 2yr-OS rate in DAC and Con group was 75.0% vs 43.0%(p=0.034), and for advanced stage AMLs, the estimated 2yr-OS rate was 66.1% vs 29.7%( p=0.031). Regarding the early relapse rate(RR) of 6 months post transplant, DAC group were less than that of Con group(11.5% vs 35.3%, p=0.124).Conclusion:1. Low-dose decitabine combined with modified BUCY is a safe and effective conditioning regimen for high-risk patients with AML/MDS with low toxicity and well tolerance.2. 100% NR patients of DAC group achieved complete remission with full donor chimerism at d30.3.Comparing with Con group, patients in DAC group had ralative lower incidence of aGVHD, TRM and RR but relative higher estimated 2-yr OS and DFS, especially for advanced stage patients. DisclosuresNo relevant conflicts of interest to declare.

ABO Mismatch Status Does Not Influence the Clinical Outcomes in Haploidentical Hematopoeitic Cell Transplantation

Background. With recent progress in modern strategies in human leukocyte antigen [HLA]-haploidentical hematopoietic cell transplantation (HCT), there has been a growing interest in the use ofhaploidentical HCT, especially when there is an urgent need to proceed to transplantation or when a donor search indicates a low likelihood of matched sibling donor (MSD) or matched unrelated donor (MUD) availability. Due to the fact that the HLA system is inherited independently of the ABO-blood group system, approximately 40-50% of allhaploidentical HCTs are performed across the blood group barrier. To the best of our knowledge, no previous studies have addressed the effect of ABO-mismatched grafts on the clinical outcomes ofhaploidentical HCTs.Methods.Our study is aretrospective cohort analysis of patients who underwent an HLA-haploidentical HCT between June 1, 2009 and April 1, 2016 at a single institution. Based on the ABO blood group, patients were placed into one of the following categories: ABO compatible, major ABO mismatch, and minor ABO mismatch. Univariate analysis was performed using χ2 test for categorical variables and Mann-Whitney Utest for continuous variables. The Kaplan-Meier estimate was implemented to compare 1-year Overall Survival rates (OS), 1-year relapse rates, cumulative incidence of 1-year acute graft versus host disease (aGVHD) of different grades, cumulative incidence of chronic GVHD (cGVHD), neutrophil engraftment, platelet engraftment, and engraftment failure rates among the three categories of patients based on ABO status. All reported P values are 2-sided, and P < .05 is considered to indicate statistical significance. A 95% Confidence Interval (CI) for the value of all outcomes of interest was reported.Results.We identified 143 patients who underwenthaplo-HCT during the study period. Of these, 91 patients were ABO compatible, 21 patients had a major ABO-mismatch status, and 27 patients had a minor ABO mismatch. Four patients had a bidirectional ABO mismatch status and were excluded from the study due to the small number. Overall, 139 patients were included in the final analysis with a median age of 51 years old (range 19-73) at the time of transplantation. 52% of the cohort was male, with 80%Caucasion, 16% African-American, and 4% belonging to other racial backgrounds. 45% of the cohort had active disease at time of transplantation, and 24% had undergone previousallo-HCTs. In the vast majority of patients (98%), G-CSF mobilized peripheral blood was used as the stem cell source. 40% of patients received amyeloablative conditioning regimen, and all patients received high dose post-transplantation cyclophosphamide as part of GVHD prophylaxis regimen.In terms of clinical outcomes, our study did not reveal a statistically significant difference between the three categories of patients based on ABO compatibility status. The 1-year OS was 49% (CI: 39-59), 52% (CI: 29-71), and 31% (CI: 14-49) for ABO compatible, major ABO mismatch, and minor ABO mismatch respectively. The 1-year relapse rate was 44% (CI: 31-56), 41% (CI: 15-65), and 42% (CI: 19-64) for ABO compatible, major ABO mismatch, and minor ABO mismatch respectively. The cumulative incidence of 1-year severeaGVHD(grade 3-4) was 13% (CI: 6-23), 14% (CI: 1-49), 6% (CI: 3-23) for ABO compatible, major ABO mismatch, and minor ABO mismatch respectively. The median neutrophil recovery time was 17 (IQR: 5), 17 (IQR: 5), and 19.5 (IQR: 10) days for ABO compatible, major ABO mismatch, and minor ABO mismatch respectively. The median platelet recovery time was 28 (IQR: 16), 27.5 (IQR: 15), and 32 (IQR: 18) days for ABO compatible, major ABO mismatch, and minor ABO mismatch respectively.Conclusion.With recent improvements in conditioning regimens and GVHD prophylaxis strategies,haplo-HCTs are becoming an increasingly available and viable option for patients without a MSD and MUD. Our retrospective cohort study, to our knowledge, is the first to examine the effect of ABO status on the clinical outcomes ofhaplo-HCTs. This study did not show any difference in clinical outcomes ofhaplo-HCTs based on major or minor ABO-compatibility status. In order to confidently conclude that ABO compatibility status does not impact the clinical outcomes ofhaplo-HCTs, well-designed prospective cohort studies with a higher number of patients are needed in the future. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Hypomethylating Agent Decitabine Prior to Chemotherapy Improves the Therapy Efficacy in Refractory/Relapsed Acute Myeloid Leukemia Patients

Introduction. Most acute myeloid leukemia (AML) patients with adverse prognosis either fail to achieve complete remission (CR) or relapse after short-term remission, new strategies are needed to improve therapeutic effect in these patients. Gene silencing via DNA methylation are frequent and reversible in high-risk AML, it provides the possibility to treat AML patients with DNA-hypomethylating agent. Decitabine alone has limited anti-leukemia effect and minimal toxicity. Studies demonstrated that decitabine prior to chemotherapy was likely to increase efficacy in AML. In this study, we investigated the effect of decitabine on susceptibility to cytotoxic drugs in chemoresistant AML cells. Efficacy and safety of decitabine prior to HAA regimen was evaluated in refractory, relapsed and high-risk AML patients.Methods. HL60, HL60/ADR, Kasumi-1, and primary AML cells were pre-treated with 1.0 μM decitabine for 72 hours, Sensitivities to harringtonine, adriamycin, cytarabine and the combination was determined by MTT, apoptosis was analyzed by flow cytometry. Protein expression was detected by western blotting. In clinic, Twenty-three patients were enrolled in decitabine prior to HAA regimen, and twenty-four patients in HAA alone. CR ratio was used to evaluate efficacy. Durations of neutrocytopenia or thrombcytopemia and infection incidence were observed to assess the safety. All of patients were followed up to 36 monthes, overall survival (OS) and disease-free survival (DFS) were calculated.Result. Decitabine increased sensitivity and apoptosis induced by harringtonine in HL60/ADR, as well as adriamycin and cytarabine in HL60/ADR and Kasumi-1 cells. But no change in sensitivity to each drug was observed in HL60, and sensitivity to harringtonine in Kasumi-1. The similar changes in sensitivity to adriamycin and cytarabine were also observed in primary AML cells from refractory patients (n=6). Cytotoxic effect of HAA was alsoincreaed by decitabine in HL60/ADR and Kasumi-1 cells (p=0.004, 0.018). Western blotting showed that decitabine decreased expression of DNMT1, activation of p53 and inhibition of c-Myc, Survivin and Bcl-2. In clinic, 16 (69.6%) patients in decitabine plus HAA regimen responded to the first course of induction therapy: 14 CR (60.9%) and 2 PR (8.7%). 1 in 2 patients with PR achieved CR after second course induction. It brought the overall CR was 65.2%. Otherwise, 10 (45.8%) patients in HAA regimen alone responded to the first induction: 7 CR (29.2%) and 4 PR (16.7%), 3 in 4 patients with PR achieved CR after the second induction, and overall CR reached 41.7%. The first-cycle CR ratio in decitabine plus HAA was higher than that in HAA alone (p=0.041). Patients continued to receive chemotherapy alternatively combined with decitabine. The median OS was 14 months in chemotherapy plus decitabine, 6 months in chemotherapy alone, and median DFS were 18 and 5 months in the former and latter. No significant difference was observed in the time of neutrophil (p=0.832, 0.631) or platelet recovery (p=0.798, 0.544) after induction and intensification therapy. The incidences of infection were also similar (p=0.724, 0.697). The clinic data indicated that decitabine plus HAA regimenit was efficacy and well-tolerated to treat refractory AML patients.Conclusion. Our results demonstrated that decitabine increased cytotoxic effect against chemoresistant AML cells. Combination of decitabine and HAA was safe and efficacy to treat refractory/relapsed AML. These findings support clinic protocols based on decitabine prior to chemotherapy to overcome resistance and improve therapeutic efficacy in AML patients. DisclosuresCarter:PrismBiolab: Research Funding.

Microtransplantation Improved Outcome in Elderly Acute Myeloid Leukemia Patients - Report from China Microtransplantation Cooperative Group

The acute myeloid leukemia in elderly patients (EAML) is always associated with low complete remission (CR) rate and a poor survival due to prolonged pancytopenia and resistance of leukemic blasts to chemotherapy. The standard or high dose induction chemotherapy improved CR rate but remission is usually transient. Nonmyeloablative allergenic stem cell transplantation shows some curative effects but associated with severe graft-versus-host disease (GVHD). Recently, our clinical studies showed that HLA-mismatched microtransplantation (MST) could increase CR rate and improve the survival but without GVHD. However, it is still lack of data and multicentre studies about MST in such patients. Here, we designed a multicentre study about microtransplantation in combination with chemotherapy in such patients and elevate effects and toxicity.Method. Total of the 148 patients with AML at the age of 60 years or over from May 2005 to May 2014, were enrolled in this study from the 11 hematology disease centers in China. The diagnosed was defined by the French-American-British (FAB) and WHO criteria. Chromosomal and immunephenotyping analyses were performed by pre-treatment of bone marrow obtained. Patients with acute promyelocytic leukemia or with a blast crisis of chronic myeloid leukemia were excluded. High risk was defined by the presence of complex cytogenetic abnormalities (with 3 or more cytogenetic abnormalities), secondary AML, or a WBC count of 50,000/µL or above. Other patients were considered at a standard risk. In accordance with the Helsinki Declaration, written informed consent for enrollment in this study was obtained from the patients or their legal guardians and the donors. Induction therapy includes cytarabine and anthracycline followed by HLA-mismatched G-CSF Mobilization HLA-mismatched donor peripheral stem cells (G-PBSC) infusion. The patients who achieved complete remission (CR) further received two courses of cytarabine as post-remission chemotherapy. None of the patients received any GVHD prophylactic treatment and further maintenance therapy. The donor and recipient HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 alleles were genotyped using a PCR-SSP method. All of 148 patients had HLA-mismatched related or unrelated donors including 126 with a family-related donor, 16 with a distantly related donor and 6 with an unrelated donor.G-PBSC infusion: the median number of mononuclear cells, CD34+ and CD3+ T cells infused per course was 2.9 (1.2-5.2)´108/kg, 1.7(1.1-4.6)´106/kg and 0.9(0.5-2.6)´108/kg, respectively.Results. Total of 148 patients were divided into three groups with 60-65 years (n=54), 66-70 years (n=41) and over 71 years (n=53). The overall CR rate was 77% and CR rate of the first cycle of induction chemotherapy was 55.3%. The CR rate was not significantly different among the patients with 60-64 years (74.1%), 65-70 years (80.4%), and over 71 years (77.4%). The CR rate was much higher in the standard group than in the high risk group (88.2% vs. 63.3%, P=0.04). The early death rate and severe infection was no significantly different among three groups. The median recovery time of neutrophils and platelets was 12d and 14d, which were not significantly different among three groups. The probabilities of 12 months OS, 24 months and 36 months were not significantly different among the patients with 60-65 years (80.9%, 60.9% and 55.8%), 66-70 years (65.4%, 46.5% and 34.9%) and over 71 years (71.3%, 30.6% and 26.8%). No definite clinical acute or chronic GVHD was observed in all of the patients but two patients who developed a severe acute GVHD and dead on day 36. A frequencies of HLA-A0201/2402WT1+CD8+ T-cells was 0.23% which is no significantly difference between the patients with low 70 years or more. The donor micro-chimerism was detected in 11 of the 18 female patients with a range of 0.0000151- 0.0386 copies of gene expression.In conclusion, the microtransplantation combined conventional chemotherapy can result in a higher CR rate and OS with a shorter duration of pancytopenia, lower severe infections and hardly no GVHD, suggested that it is a much safer and effective new therapy for elderly AML patients including those who over 70 years old. DisclosuresNo relevant conflicts of interest to declare.

Better High Resolution HLA-Matching Is Associated with Lower Transplant Related Mortality after Cord Blood Transplantation

Background: For patients lacking a suitable related or unrelated stem cell donor, cord blood (CB) as the source of stem cells is being increasingly utilized both in pediatric and adult patients. A CB graft is attractive due to the increased level of HLA disparity that can be tolerated, allowing nearly all patients to find a donor. HLA-typing is performed minimally at the antigen level for HLA-A and -B (low resolution LR), and high resolution (HR) HLA-typing is performed for HLA-DRB1 alleles. More recently, many centers are turning to HR HLA-typing as the standard; however the impact on outcomes of HLA disparity using HR typing has not been clearly determined.Methods: The impact of HR HLA matching was retrospectively analyzed on 202 patients with hematologic malignancies receiving either a single or double cord blood transplant (CBT) between 2007-2014 at the Hutchinson Center. 135 patients (67%) had HR typing for HLA-A, -B, -C, and -DRB1. For double CBT, the HR HLA typing of the predominant cord was used in the outcome analysis. Patients with mixed chimerism (n=2) or graft failure (n=9) were excluded leaving a total of 124 patients (61%) in the final analysis. HR typing at 4 loci revealed that the median HLA match was 5/8 (range 2-7/8). The cause-specific hazards of failure for each endpoint were compared between patients with worse HR typing (≤ 4/8 HR HLA match, n=46) and patients with better HR typing (≥5/8 HLA match, n=78). These models were adjusted for various factors: patient age, weight, risk of disease, presence of minimal residual disease (MRD), patient CMV serostatus, conditioning regimen (myeloablative vs. non-myeloablative), and grades III-IV acute graft-vs.-host disease (aGVHD).Results: The median patient age and weight were 43 years and 76 kg and 33 years and 69 kg for the ≤ 4/8 and ≥5/8 groups respectively (p=0.03, p=0.06). The two groups were similar with respect to conditioning intensity, sex, race, CMV serostatus, MRD status, and diagnosis (Fig. 1). The median pre-thaw TNC/kg x107 and pre-thaw CD 34 cells/kgx106 values (Fig. 1) indicated that there was no difference between the two HR HLA groups in regards to both CB unit size or stem cell content (p=0.25). Median time of neutrophil recovery was 20 days for ≤ 4/8 group and 19 days for ≥5/8 group with a cumulative incidence of engraftment of 93% and 98% respectively (p=0.20). The median time to platelet recovery (>20 x 109/L) was also similar between the two groups: 34 days for the ≤ 4/8 group and 35 days for the ≥5/8 group (p=0.12). The probability of 4-year DFS was 34% and 62%, respectively (p=0.04) (Fig. 2A). The cumulative incidence of transplant related mortality (TRM) at 4 years was 41% for the ≤ 4/8 group and 15% for the ≥5/8 group (p=0.002) (Fig. 2B). In multivariable analysis the association between worse HLA-matching and higher TRM remained statistically significant [HR=3.22, 95% CI: 1.25-8.20, p=0.01]. The most common causes of death were pulmonary failure (27%), bacterial or fungal infection (24%), and multi-system organ failure (21%). Interestingly, worse HLA matching did not reduce the risk of relapse [HR=0.87, 95% CI: 0.32-2.4, p=0.80] or increase the risk of grades III-IV aGVHD (p=0.45).Conclusion: Our study demonstrates that TRM was significantly lower in patients receiving a ≥5/8 HR HLA engrafting CB unit leading to a better DFS. The increased incidence of TRM in the less HLA-matched group was not due to an increased risk of aGVHD. Our results support that the use of ≥5/8 allele-matched HLA-units is associated with better outcomes; however how to select CB units based on HLA-allele match in the setting of double CBT still needs to be confirmed in larger studies analyzing how HLA-mismatch at different loci (patient vs. units and unit vs. unit) can impact CB unit selection and dominance. [Display omitted] [Display omitted] DisclosuresDelaney:Novartis: Other: Chair, DSMB; Biolife Solutions: Membership on an entity's Board of Directors or advisory committees; medac: Research Funding.

Clinical Analysis of Cytomegalovirus Infection after Different Patterns of Hematopoietic Stem Cell Transplantation

To investigate the clinical difference of cytomegalovirus (CMV) infection between HLA-matched allogeneic hematopoietic stem cell transplantation (allo-HSCT) and haploidentical hematopoietic stem cell transplantation (hi-HSCT). The clinical data of 83 patients who had undergone allo-HSCT were retrospectively analyzed. Out of them 50 patients underwent hi-HSCT and 33 patients received grafts from HLA-matched donors. The sera of all recipients and donors were CMV-negative before transplantation. All patients accepted myeloablative regimen without total body irradiation. PCR was performed to detect CMV in the peripheral blood twice a week after neutrophil recovery. CMV-DNA>500 copies/ml was defined as CMV viremia. 68 patients (81.9%) were diagnosed as CMV viremia before 100 days after transplantation. The incidence of CMV infection in hi-HSCT group was 90% and significantly higher than that in HLA-matched HSCT group (69.7%) (P < 0.05). All the patients responded well to anti-CMV therapy; however, 63 cases experienced CMV reactivation. The occurrence rate of CMV reactivation in hi-HSCT group (95.6%) was comparable to that in HLA-matched HSCT group (87.0%) (P > 0.05). Univariate analysis showed that the transplantation pattern, the recovery time of peripheral neutrophils and the occurrence of acute graft-versus-host disease (aGVHD) significantly related to the episode of CMV viremia, while the sex and age of the recipients, and the recovery time of platelets did not associate with the incidence. Further analysis found that the recovery time of neutropils and platelets in HLA-matched HSCT group were greatly shorter than those in hi-HSCT group (P < 0.05). The incidence of aGVHD was comparable between two groups however, incidence of severe aGVHD was significantly higher in hi-HSCT (P < 0.05). The hi-HSCT is more susceptible to CMV infection, which may be related to the higher incidence of severe aGVHD and the relative delay of hematopoietic reconstruction as compared with HLA-matched HSCT.

Efficacy of plerixafor in children with malignant tumors failing to mobilize a sufficient number of hematopoietic progenitors with G-CSF.

Mobilization of suitable amounts of PBSCs with granulocyte-CSF (G-CSF) can be difficult in children. We report the results of using plerixafor in pediatric patients who failed to mobilize progenitors with G-CSF-based regimens. Thirty-three patients, median age 9 years (range 1-18 years) and median weight 29 kg (range 10-85 kg) were enrolled into the study. After 4 days of G-CSF stimulation, the median CD34+ cell count in peripheral blood was 10.4 per μL (range 0.27-23.0 per μL). Plerixafor was administered subcutaneously (0.24 μg/kg in 30 patients and 0.3 μg/kg in 3 patients) 11-12 h before apheresis. At the time of apheresis, CD34+ cell counts increased to a median of 44.1 per μL (range 8.4-357.0 per μL), a median 4.4-fold increase. Two patients (6%) failed to mobilize. Thirty-one patients underwent apheresis and in 27 >2 × 10(6) CD34+ cells per kg of body weight were collected after one procedure. In total, 31 of 33 patients mobilized successfully and the median number of cryopreserved CD34+ cells was 5.6 × 10(6) /kg body weight (2.7 × 10(6)-27.4 × 10(6)). Twenty-four patients underwent transplantation. Engraftment was achieved in all but one patient, who died on day +9 after hematopoietic stem cell transplantation. The median time of neutrophil and platelet recovery was day +12 and +16, respectively. Our study confirms that plerixafor has impressive efficacy and very modest toxicity in children.

Rebound Thrombocytosis following Induction Chemotherapy Is an Independent Predictor of a Good Prognosis in Acute Myeloid Leukemia Patients Attaining First Complete Remission

There are very few data about the relationship between acute myeloid leukemia (AML) prognosis and bone marrow recovery kinetics following chemotherapy. In this study, we aimed to assess the prognostic importance and clinical associations of neutrophil and platelet recovery rates and rebound thrombocytosis (RT) or neutrophilia (RN) in the postchemotherapy period for newly diagnosed AML patients. De novo AML patients diagnosed between October 2002 and December 2013 were evaluated retrospectively. One hundred patients were suitable for inclusion. Cox regression analysis using need for reinduction chemotherapy as a stratification parameter revealed RT as the only parameter predictive of OS, with borderline statistical significance (p = 0.06, OR = 7; 95% CI 0.92-53), and it was the only parameter predictive of DFS (p = 0.024, OR = 10; 95% CI 1.3-75). In order to understand whether RT or RN was related to a better marrow capacity or late consolidation, we considered neutrophil recovery time and platelet recovery time and nadir-first consolidation durations in all patients in the cohort. Both the marrow recovery duration and the time between marrow aplasia and first consolidation were shorter in RT and RN patients. To our knowledge, this is the first study to report a correlation between RT/RN and prognosis in AML.

Allogeneic hematopoietic stem cell transplantation in children with aplastic anemia.

The aim of this study was to prospectively investigate the efficacy and safety of fully matched allogeneic hematopoietic stem cell transplants in children with severe aplastic anemia in China. A total of twenty patients with severe aplastic anemia were enrolled in our study. Thirteen cases underwent transplantation with fully human leukocyte antigen (HLA)-matched, granulocyte-colony stimulating factor (G-CSF)-primed bone marrow and peripheral blood stem cells (PBSCs) from matching sibling donors. One patient received fully HLA-matched bone marrow from an unrelated donor. Six patients received fully HLA-matched G-CSF-primed PBSCs from unrelated donors. The conditioning regimen included fludarabine, cyclophosphamide, and rabbit anti-thymocyte globulin. Graft-versus-host disease prophylaxis was conducted with cyclosporin A and short-course methotrexate. The median follow-up duration was 3.08 years (range, 0.83-8.41years). The median time of neutrophil recovery (>0.5 x 10(9)/L) was 14 days (range, 10-20 days), and the median time of platelet recovery (>20 x 10(9)/L) was 19 days (range, 14-31 days). The survival rate at the cutoff point of follow-up was 95.0% (19/20). Initial engraftment rate was 95% (19/20). Late graft failure (graft failures occurring 1 year or longer after transplantation) was observed in one patient. Only one patient developed Grade I acute graft-versus-host disease. Two cases suffered from Epstein- Barr virus (EBV)-associated post-transplant lymphoproliferative disorder and remitted after treatment with rituximab. One patient was diagnosed with hyperthyroidism 2.5 years after transplantation. Our study indicated that allogeneic hematopoietic stem cell transplantation is an effective and safe treatment for children with severe aplastic anemia in China.

Rebound Thrombocytosis Is an Independent Predictor of Good Prognosis in AML Patients Attaining First Complete Remission

We investigated the prognostic importance and clinical associations of neutrophil and platelet recovery rates and rebound thrombocytosis (RT) or neutrophilia (RN) in post-chemotherapy newly diagnosed AML patients. De novo AML patients who were diagnosed between October 2002 and December 2013 were evaluated retrospectively. The patients who attained first complete remission (CR) after one or two induction therapies were selected and their marrow aplasia periods preceding CR were considered. The patients who were transplanted were excluded. Neutrophil (NRT) and platelet recovery times (PRT) were accepted as the periods between neutrophil nadir and ³1000/µl neutrophil count and platelet nadir and ³50000/µl platelet count, respectively. The platelet nadir-to-first consolidation (PCT) and neutrophil nadir-to-first consolidation times (NCT) were computed. RN and RT thresholds were accepted as 7000/µl and 450000/µl respectively.There were 100 patients suitable for inclusion. The frequency of RT was 11/31, 6/19, 5/50 in patients with favorable ELN cytogenetic categories, normal karyotype, other cases, respectively (p=0.1). Cox regression analysis using need of reinduction therapy as stratification parameter revealed RT as the only parameter predicting both OS (p=0.06) and DFS (p=0.024). After understanding that RT525 (threshold 525000/ µl) is an independent prognostic parameter in AML patients, we tried to find its prognostics value in subgroups. There were 15 APL patients. Prognostic value of RT525 could not be determined due to low event rates. Only two patients experienced an event. Both events were mortalities during consolidation. There was one mortality in RT525 and no- RT525 groups each. There were 16 CBF-type AML patients. Four patients experienced an event. All events were relapses. All four events occurred in 12 cases without RT525 while none of four patients with RT525 experienced an event. However, statistical significance was not observed between groups in DFS (figure 1) and OS comparisons due to low event rates (p=0.17 and p=0.18 respectively). In other AML patients, there were 35 events (25 relapse, 10 deaths in CR). All of the events occurred in no-RT525 group. All RT525 cases in this group were living with CR at last follow-up. Both DFS (median [95% confidence interval] not reached versus 13.2 (6.1 - 20.2) months, p=0.004) (figure 2) and OS (not reached versus 17.0 (0 - 34.6) months, p<0.001) rates were higher in RT525 cases. In order to understand whether RT or RN were related to better marrow capacity or late consolidation, we considered NRT and PRT and nadir-first consolidation durations in all patients cohort. For RT group, the PRT was 10.3±5.2 days whereas it was 12.8±8.5 days for no-RT group (p=0.43). The NRT was 15.8±7.8 and 20.3±9.7 days in RN and no-RN groups respectively (p=0.07). For RT group, the PCT was 27.8±7.9 whereas it was 29.1±15.2 days for the group with no-RT (p=0.07). NCT was 30.2±11.2 and 34.6±18.2 days for RN and no-RN groups respectively (p=0.12). Both the marrow recovery duration and the time between marrow aplasia and first consolidation were shorter in RT and RN patients.To our knowledge, this is the first study that reports a correlation between RT/RN and prognosis in AML. Interestingly, RT was the only significant independent parameter in multivariate analyses also including classical prognostic risk factors for OS and DFS. The favorable prognosis associated with RT525 was evident in AML patients other than APL and CBF-type disease. However it could not be demonstrated in APL and CBF-type disease probably due to low event rates. In accordance with this suggestion there was a trend towards statistical significance in CBF-type disease (0/4 versus 4/12 relapses in RT525 and no-RT525 cases respectively, p=0.17). The marrow recovery time and the duration between marrow aplasia and first consolidation were shorter in RT and RN cases indicating better healthy hematopoiesis/marrow capacity in this group. As RT and RN are very easy to detect, they can be used as prognostic indicators in countries with limited laboratory facilities. These findings should be confirmed in other patient cohorts and preferably prospective studies. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.