Interobserver Variability with the Diagnosis of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) ¿Is the Threshold of 20% Bone Marrow Blasts Reproducible?

Introduction. The boundaries between MDS and AML are still a matter of debate. In the 2001 WHO Classification, the myeloblast count distinguishing AML and MDS was lowered from 30% to 20% of the bone marrow (BM) cells or peripheral blood (PB) leukocytes. It was justified on the basis that treating patients with 20-29% BM blasts with intensive chemotherapy showed a similar outcome to those with > 30% BM blasts. However, the better knowledge of the biology of both diseases is showing that in several cases AML and high risk MDS share identical genetic profiles, as it is well known in AML with myelodysplasia- related changes (AML-MRC). Currently there are new therapeutic options, less toxic, and suitable for elderly people.The threshold of 20% BM blast is artificial, but it is still the main criterion used in clinical trials and also in real life to discriminate patients that probably belong to the spectrum of the same biological entity. Treatment of patients with MDS or AML is widely based in this relatively arbitrary condition. Objective: To study if the threshold of 20% bone marrow blasts, distinguishing MDS with excess of blasts type 2 (MDS EB 2) and AML, is reproducible among different observers. Methods. 120 bone marrow samples from patients previously diagnosed with MDS-EB-2, AML or therapy-related myeloid neoplasms (t-MN) according to 2016 WHO classification were included. The diagnosis of MDS required cytogenetics and/or FISH, and the cases with AML should have been classified following the 2017 ELN recommendations, regarding immunophenotyping, cytogenetics and molecular biology. The design of the study was established to include cases with <40% BM blasts, WBC <25x109/L and less than 20% myeloblasts in peripheral blood. The proportion of samples from each category was not predefined. Specimens were collected from 12 hospitals and were evaluated by 12 morphologists. Each observer evaluated 20 samples, and each sample was analyzed independently by two morphologists. The second observer was blinded to the clinical and laboratory data, except for the peripheral blood (PB) counts. The interobserver concordance was evaluated using the Cohen kappa test. Results. Finally 116/120 samples were considered suitable for the study. Regarding 2016 WHO categories, 55 cases showed MDS EB-2, 44 AML-MRC, 8 t-MN, 4 AML- NOS, 2 NPM1-mutated AML, 2 RUNX1-RUNX1T1 AML, 1 BCR-ABL1+ AML. Next generation sequencing was performed in 79 cases. Discordance was observed in 34/116 cases (29.3%). 14 cases with MDS-EB2 (1 NPM1+) were classified as AML-MRC by the second observer, 16 AML cases as MDS EB-2, 3 MDS EB-2 as MDS- EB1 and 1 AML as MDS- EB1. The genetic and /or molecular profile of the discordant cases was heterogeneous. Regarding the threshold of 20% BM blasts, discrepancies were 31/116 (26.7%, I Kappa test = 0.46, moderate agreement). The agreement between MDS-EB-2 and AML-MRC, with discordance in 28/98 cases (28.6%), was moderate-fair (Kappa test= 0.42). Conclusion. The threshold of 20% BM blasts did not accurately separate AML from MDS EB-2. Particularly less concordance was seen for AML-MRC. Incorporation of genetic and molecular characteristics to the morphologic diagnosis is needed to optimize the definition of both entities. Acknowledgment: Angel Cedillo, Secretaría Técnica AMHH. Disclosures Font Lopez: GILEAD: Membership on an entity's Board of Directors or advisory committees; CELGENE-BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Loscertales: Janssen, Abbvie, Astra-Zeneca, Beigene, Roche, Gilead: Consultancy; Janssen, Abbvie, Roche, Gilead: Speakers Bureau. Cedena: Janssen, Celgene and Abbvie: Honoraria.

Impact of Post-Remission Maintenance Therapy (MT) on Outcomes in Patients (pts) with Newly Diagnosed Acute Myeloid Leukemia (AML) in Real-World Practice

INTRODUCTION : Therapeutic advances have led to improved survival outcomes in patients (pts) with AML. Consolidation therapy helps to eradicate residual leukemia and prevent relapse. However, relapse remains a major concern and contributes to suboptimal outcomes in pts with newly diagnosed AML who attain remission following induction chemotherapy (IC). Strategies for maintenance therapy (MT) attempt to prolong AML remission and extend survival. MT approaches have included chemotherapy, hypomethylating agents (HMAs), and targeted small-molecule drugs. Overall, the evidence in favor of MT is limited. The oral formulation of azacitidine (Oral-AZA), an HMA, is the first and only MT to demonstrate significant overall survival (OS) and relapse-free survival (RFS) benefits in pts with a broad range of AML subtypes (Wei, NEJM 2020), leading to regulatory approvals in the United States (2020), Canada (2021), and European Union (2021). This study aimed to determine in real-world practice whether the use of MT after IC, with or without consolidation, conferred any clinical advantage before Oral-AZA became available. METHODS: This study included pts in the US-based Flatiron TM Health cancer-specific electronic health record-derived database diagnosed with AML between January 2014 and December 2020. Eligible pts in this study obtained remission (< 5% bone marrow blasts) from first-line (1L) induction chemotherapy or venetoclax (VEN)-based therapy, had not previously taken Oral-AZA or any clinical study drug, and did not undergo transplant prior to relapse. Pts were grouped into 2 cohorts: Cohort A comprised pts who did not receive MT, and Cohort B comprised pts who did receive MT. RFS and OS were estimated using Kaplan-Meier (KM) methods. Multivariate Cox regression models that retained baseline (BL) characteristics (age, sex, BMI, ECOG performance status [PS], and cytogenetic risk) were used to examine the relationships between use of MT and relapse (> 5% bone marrow blasts), and MT and survival. RESULTS: A total of 952 pts met the selection criteria: 808 pts (84.9%) in Cohort A and 144 pts (15.1%) in Cohort B. The most commonly received MTs for pts in Cohort B were injectable AZA (34.7%; n = 50), decitabine (24.3%; n = 35), and VEN-based regimens (21.5%; n = 31). Cohorts A and B were comparable for sex, BL BMI, ECOG PS score, and practice type (Table). Pts who did not receive MT (Cohort A) were younger (mean age 62.1 vs 66.0 years; P = 0.006) and more commonly presented with favorable cytogenetic risk (17.2% vs 6.9%; P = 0.011) compared with pts who received MT (Cohort B). The percentage of pts receiving IC in a 7+3 regimen was similar between Cohort A and Cohort B (69.1% vs 67.4%, respectively; P = 0.685), as were the proportions of pts receiving VEN + an HMA (23.3% vs 17.4% P = 0.118). The KM analysis indicated that although median RFS of Cohort A was longer than Cohort B, differences between cohorts were not statistically significant (303 vs 276 days, P = 0.175). In a subanalysis of pts with intermediate/poor cytogenetic risk, median RFS was 201 days for Cohort A and 230 days for Cohort B (P = 0.952). In the multivariate Cox model, treatment with MT was not a significant predictor of improved RFS vs no MT (hazard ratio [95% CI]: 0.97 [0.79, 1.20]). Age and cytogenetic risk were significantly associated with RFS. The median OS was 659 days for Cohort A and 389 days for Cohort B (P = 0.006). In the subanalysis excluding pts with favorable or unknown cytogenetic risk, median OS was 400 days for Cohort A and 366 days for Cohort B (P = 0.561). A multivariate Cox regression model suggested that treatment with MT was not a significant predictor of improved OS (hazard ratio [95% CI]: 0.88 [0.70, 1.10]). Age, sex, ECOG PS, and cytogenetic risk were all significantly associated with OS. CONCLUSIONS: These Flatiron data provide real-world evidence that despite decades of study, optimal MT in AML had remained elusive. Prior to approval of Oral-AZA, the most common MT options for pts with AML in first remission after 1L induction therapy were limited and appeared to lack clinical benefit. Pts with AML need an MT that prolongs remission and improves long-term survival. Further research is needed to elucidate the benefits and disadvantages of different MT options and may lead to establishment of optimal MT as standard of care. Figure 1 Figure 1. Disclosures Potluri: Bristol Myers Squibb: Consultancy. Rotter: SmartAnalyst Inc.: Current Employment. Chen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.

Venetoclax Plus Hypomethylating Agent for the Salvage Treatment of Myeloid Malignancies Relapsing after Hematopoietic Stem Cell Transplantation: A Multicenter Retrospective Study on Behalf of the Zhejiang Cooperative Group for Blood and Marrow Transplantation

Objective Hematopoietic stem cell transplantation (HSCT) is one of the most efficient treatments for hematologic malignancies. However, relapse remains the main cause of transplant failure. In myeloid neoplasia, the long-term survival for patients who relapsed after HSCT ranges from 10% to 20%. Conventional chemotherapy and donor lymphocyte infusion (DLI) exhibit limited effect and are accompanied by high risks of infection and graft versus host disease (GVHD). New, less toxic, and more efficient treatment options are urgently needed. Venetoclax (VEN), a selective inhibitor of anti-apoptotic protein Bcl-2, combined with hypomethylating agents (HMAs) was well-tolerated and showed an impressive response rate in elderly patients with AML, both as frontline therapy and for relapse. While in post-transplant relapsed patients, the efficacy of the combination of VEN and HMA (VEN-HMA) still needs to be explored. Methods Between July 2018 and May 2021, forty-two patients who experienced post-transplant relapse were retrospectively analyzed in this study. All these patients received at least one cycle of VEN-HMA. The salvage therapy consisted of VEN for 28 consecutive days (100 mg of VEN for the first day and 200 mg for the second day, then increased to the final dose of 400 mg daily or equivalent with azole co-administration). Thirty-nine patients received azacytidine (100mg/m2, d1-7) while the other 3 patients were given decitabine (10mg/m2, d1-5) in combination with VEN. Disease types included acute myeloid leukemia (AML, n=32), myelodysplastic syndrome (MDS, n=7), chronic myelomonocytic leukemia (CMML, n=2) and chronic myeloid leukemia (CML, n=1). 28 (66.7%) patients achieved complete remission before transplantation and 14 (33.3%) patients were transplanted in a non-remission status. Haploidentical-related donor (HID, n=31) was the most common donor type, followed by matched sibling donor (MSD, n=6) and unrelated donor (URD, n=5). Each patient was analyzed for chromosomal and genetic abnormalities either at diagnosis and at post-transplant relapse. Complex/monosomal karyotype was seen in 10 (23.8%) patients. 9 (21.4%) patients had TP53 mutation or deletion and 7 (17.9%) had IDH1/2 mutation. The median time from transplantation to relapse was 329 (range, 30-1584) days, 27 (64.3%) patients had an early relapse (within 1-year post-HSCT). 16 (38.1%) patients developed acute GVHD and 15 (35.7%) developed chronic GVHD before relapse. 24 (57.1%) patients received VEN-HMA as first-line salvage therapy, while the other 18 (42.9%) patients received this combination therapy after failure with chemotherapy or DLI. 22 (52.4%) patients had a higher tumor burden (bone marrow blasts >20%) at the initiation of VEN-HMA. In total, 20 (47.6%) patients responded to the VEN-HMA therapy with a reduction in bone marrow blasts. 14 (33.3%) patients fulfilled the criteria of CR/CRi and all of them achieved the best response in the first cycle of VEN-HMA. However, 4 (9.5%) patients even experienced disease progression after VEN-HMA. After a median follow-up time of 84 (18-535) days, patients who achieved CR/CRi experienced a significantly higher overall survival (OS) than those who did not (85.7% vs 14.3%, p <0.0001). In univariate and multivariate analysis, we found that early relapse (HR=4.000, p=0.046) was the only independent risk factor that influenced the CR/CRi rate. Conclusion VEN-HMA is safe and efficacious for patients with myeloid malignancies relapsing after transplantation. Patients relapsing within 1-year post-transplantation may be more likely to benefit from this combination therapy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Influence of platelet count at diagnosis and during the course of disease on prognosis in MDS patients

Thrombocytopenia at diagnosis and platelet drop within the first 6 months have an adverse effect on prognosis of MDS patients. We therefore were interested in the association and impact on prognosis of morphologic findings of megakaryocytes and platelets with platelet count at diagnosis, bleeding complications, and the drop of platelets during the course of disease. This retrospective analysis was based on 334 MDS patients from the Duesseldorf MDS registry that were followed up for blood counts, bleeding, transfusion dependency, and AML evolution and correlated with morphology of the megakaryocytes and platelets. Thrombocytopenia was found more frequently in higher risk MDS and was associated with hypocellularity of the megakaryocytes in the bone marrow. Signs of bleeding were present at diagnosis in 14% and occurred during the disease in 48% of all MDS patients. Death due to bleeding was ranked third behind infections and AML. A decrement of platelets during the first 6 months was associated with an inferior overall survival of 21 vs. 49 months and with a higher cumulative 2-year AML rate of 22.2% vs. 8.3% (p = 0.001). In a multivariate analysis, besides bone marrow blasts and karyotype, decreasing platelets were also associated with an inferior outcome. Signs of bleeding are present in a relevant number of MDS patients and account for significant morbidity and mortality in MDS. We could demonstrate the prognostic importance of decreasing platelets during the course of disease in all MDS patients, identifying patients at higher risk for death or AML progression.

Clinical characteristics and the treatment outcome in patients with acute lymphoblastic leukemia

Introduction: Acute lymphoblastic leukemia (ALL) is the malignant transformation and proliferation of lymphoid progenitor cells. The disease outcome is significantly influenced by cytogenetic and molecular characteristics, leukocyte levels, the percentage of blood and bone marrow blasts, infiltration of the CNS, and the modality of the applied therapy. Aim: Determining clinical, immunophenotypic, and cytogenetic characteristics of patients with ALL; ascertaining remission rates, the presence of resistant forms, the rates of relapse and overall survival (OS); determining prognostic factors for patient survival. Materials and methods: This five-year retrospective study included 74 patients. The study covered the period from November 2013 to October 2018. The influence of sex, age, immune subtype of ALL, leukocyte levels, percent of blood and bone marrow blasts, and cytotoxic-molecular characteristics on survival were analyzed. Results: A total of 56 (75.0%) patients had B-cell ALL, while 18 (25.0%) patients had T-cell ALL. The average age was 49.5 years (20 - 77). Complete remission was achieved in 54 (72.9%) patients, 40 (71.4%) B-cell ALL patients and 14 (77.7%) T-cell ALL patients. Refractory leukemia was confirmed in 7 (9.4%) ALL patients, 5 (8.9%) B-cell ALL patients and 2 (11.1%) T-cell ALL patients. Mortality during induction was observed in 13 (17.56%) patients, 8 (14.2%) B-cell ALL patients and 5 (27.7%) T-cell ALL patients. Relapse occurred in 25 (46.3%) patients, 20 (47.5%) B-cell ALL patients and 5 (33.3%) T-cell ALL patients. Univariate analysis showed that an unfavorable outcome was associated with age ≥50 years (p < 0.001), COP chemotherapy (p < 0.001), non-transplant patients (p = 0.011), and infiltration of the CNS (p < 0.001). Conclusion: Survival in ALL patients is significantly affected by patient age, modality of applied therapy, and infiltration of the CNS by disease.

Successful Treatment of Concurrently Diagnosed Multiple Myeloma and Myelodysplastic Syndrome with Isolated Del(5q) with Lenalidomide, Bortezomib, and Dexamethasone

Lenalidomide is known to be an effective therapy for multiple myeloma (MM) and for myelodysplastic syndrome with isolated del(5q). However, there have been very few reports of treatment of both conditions using lenalidomide when they are diagnosed concurrently. A review of the literature revealed two reports of MM and del(5q) MDS treated with lenalidomide. We report the case of a patient simultaneously diagnosed with multiple myeloma and myelodysplastic syndrome with isolated del(5q) who was treated successfully with lenalidomide. The patient is a 74 year old female who was referred to hematology for worsening chronic macrocytic anemia with a hemoglobin of 9.4 g/dL. A serum protein electrophoresis (SPEP) was obtained during her workup and demonstrated an IgG kappa monoclonal spike of 4.7 g/dL. Free light chain analysis demonstrated a kappa/lambda ratio of 36.7. The patient was mildly hypercalcemic at 10.6 g/dL but had no renal insufficiency. Platelet and white blood cell counts were normal. There were no osteolytic lesions on skeletal survey and a whole body PET scan identified no bony disease or plasmacytomas. A β-2 microglobulin level was 3.7 mg/L and albumin was 3.3 g/dL. Bone marrow biopsy revealed 60% plasma cells in a 70% cellular marrow. Granulocytic and megakaryocytic dysplasia was identified. Fluorescence in situ hybridization returned showing a 4:14 translocation in 72% of analyzed nuclei and monosomy 13 in 61% of nuclei analyzed consistent with an unfavorable risk profile. Chromosome analysis also revealed a 5q deletion in 15 of 20 analyzed cells. Bone marrow blasts were measured at 1%. Therefore, the patient concurrently met diagnostic criteria for stage II IgG kappa multiple myeloma per the International Staging System and low risk myelodysplastic syndrome with isolated del(5q) per the 2016 WHO classification of MDS with a Revised International Prognostic Scoring System Score (IPSS-R) of 2. She was started on lenalidomide 25 mg daily, bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 and dexamethasone 20 mg on days 1, 8, and 15 of a 21 day cycle. After 3 cycles of therapy, serum immunofixation electrophoresis showed an unquantifiably low IgG kappa monoclonal spike and the patient's kappa/gamma light chain ratio had normalized to 1.1. Hemoglobin and calcium returned to normal. On repeat bone marrow biopsy, there was normocellular marrow with 4% polytypic plasma cells by kappa/lambda immunohistochemistry. No dysplasia was identified and bone marrow blasts were 1.5%. Therefore, the patient achieved a very good partial response (VGPR) to therapy for multiple myeloma according to International Myeloma Working Group criteria within 3 months. She met National Comprehensive Cancer Network criteria for response of her MDS to lenalidomide by normalization of hemoglobin. The patient's case demonstrates successful treatment of concurrently diagnosed multiple myeloma and MDS with isolated del(5q) using lenalidomide. Among the two other similar cases we discovered in the literature, one patient was treated with low-dose lenalidomide and dexamethasone [Nolte, et al. Eur J Haematol. 2017 Mar;98(3):302-310.], and the other patient was treated with high-dose lenalidomide and dexamethasone, achieving a partial response [Ortega, et al. Leuk Res. 2013 Oct;37(10):1248-50.]. Neither patient received a proteasome inhibitor. In our case, the patient was treated with higher intensity induction therapy for multiple myeloma and achieved a VGPR. She did not have worsening cytopenias during therapy, and in fact experienced normalization of her blood counts. Therefore, it is reasonable to treat patients simultaneously diagnosed with MM and MDS with isolated del(5q) with standard three-drug induction therapy for multiple myeloma. While our approach makes sense in the abstract, hematology/oncologists should be aware that it works in practice. Disclosures No relevant conflicts of interest to declare.

Physicians' Experience in Blood Supply Shortages and the Top Factors That Impact the Clinical, Economic, and Humanistic Outcomes of Myelodysplastic Syndrome (MDS) Patients in 5 European Countries

Introduction: Among patients with MDS, it is estimated that 17-82% (median 60%) are transfusion dependent (Harnan S, et al. Acta Haematol 2016;136:23-42) and require ≥ 1 unit of red blood cells (RBCs) every 8 weeks. Sufficient blood supply is essential for the administration of RBC transfusions in patients with MDS, as shortage of blood supply may create unnecessary burden, such as treatment delay, worsened quality of life, or increased healthcare utilization. To our knowledge, no studies have examined the physicians' experience associated with shortage of blood supply and RBC transfusion delays in this patient population. Physicians' perspectives on the factors that impact clinical, economic, and humanistic outcomes of patients with MDS are also not well understood. The current study investigated physicians' understanding of these topics. Methods: Prior to data collection, interviews were conducted with physicians (3 each in France, Germany, Italy, Spain, and the UK) to pre-test and revise the questionnaire, a 40-minute web-based physician survey via the M3 Global Research physician panel, for relevance and understanding. All physicians took the survey in their native language and had to have been in practice for 2-35 years, spend ≥ 75% of their time in direct patient care, and have managed ≥ 15 patients with MDS in the past 3 months. Physicians answered questions regarding adequacy of blood supply related specifically to RBC transfusions for patients with MDS. Physicians identified the top 10 factors (from a list of 32) impacting the clinical, economic, and humanistic outcomes of patients with MDS. These factors were then weighted accordingly (assigned point values summing up to 100). Results were described descriptively in proportions for categorical/ordinal data and mean (standard error [SE])/95% confidence intervals [CI]) for continuous data. Results: A total of 244 hematologist/oncologists, 124 hematologists, and 10 oncologists completed the survey in France, Germany, Italy, Spain, and the UK (n = 75 [approx.] in each country; Table). On average, physicians were in clinical practice for 14.70 years (SE 0.32), 41.3% were aged 45-54 years, and 64.3% were male. Physicians spent 88.7% (SE 0.36%) of their professional time in patient care, and had seen an average of 54.5 (SE 2.26) patients with MDS in the past 3 months. Over 65% of physicians (range 54.7 [France]-73.7% [UK]) reported that their patients with MDS encountered RBC transfusion delays due to blood supply shortage (Table). On average this impacted 9.0% (95% CI 7.6-10.4) of all patients with MDS. However, among physicians who reported delays (n = 248), 13.8% (95% CI 11.9-15.7) of patients were impacted, ranging from 11.0% (Spain) to 19.4% (Italy). Physicians (17.2%; range 9.3 [Spain]-31.6% [Italy]) reported ≥ 25% of their patients with MDS requiring transfusions experienced transfusion delay due to blood supply shortage. On average, patients experienced a 4.2-day (95% CI 3.6-4.8) delay in receiving a transfusion due to blood supply shortage, and 16.7% (95% CI 14.3-19.1) of patients required additional healthcare provider visits due to blood supply shortages. The top 10 factors reported that impact clinical, economic, and humanistic outcomes of patients with MDS included: Eastern Cooperative Oncology Group performance status (ECOG PS) (74.6%); age (66.7%); hemoglobin level (66.7%); infections (61.1%); percentage bone marrow blasts at diagnosis (60.1%); comorbidities (59.5%); platelets (56.3%); cardiovascular comorbidity (52.9%); genetic abnormalities (50.3%); and white blood cell count (48.4%). Factors that had the greatest mean impact scores were ECOG PS (8.9, 95% CI 8.1-9.8); percentage bone marrow blasts at diagnosis (8.3, 95% CI 7.3-9.2); age (7.2, 95% CI 6.5-8.0); hemoglobin level (6.8, 95% CI 6.1-7.4); and comorbidities (6.6, 95% CI 5.9-7.3). Conclusions: Two thirds of physicians reported that shortage of blood supply resulted in a delay in RBC transfusions for patients with MDS. Almost 20% reported ≥ 25% of their patients with MDS requiring transfusions experienced a transfusion delay due to blood supply issues. ECOG PS, hemoglobin level, and age were the top factors reported to impact outcomes of patients with MDS. New treatment options should be explored to help reduce the number of RBC transfusions, which may also help improve clinical, economic, and humanistic outcomes of patients with MDS. Disclosures Gupta: Bristol Myers Squibb: Consultancy, Research Funding; Kantar: Current Employment. Kulasekararaj:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees. Constantino:Kantar: Current Employment. Grisolano:Kantar: Current Employment; Bristol Myers Squibb: Consultancy. Tang:Bristol Myers Squibb: Current Employment; Asclepius Analytics: Current Employment. Jones:Bristol Myers Squibb: Current Employment. Tang:BMS: Current Employment, Current equity holder in publicly-traded company.

Does a Change in IPSS-R between Diagnosis and Transplant Have an Impact on Transplant Outcome in Patients with MDS? a Retrospective Analysis from the EBMT Chronic Malignancies Working Party

IPSS-R is a well established prognostic factor for transplant outcome in patients with MDS, irrespective whether it is assessed at diagnosis or at transplant. However it is unclear how a change in IPSS-R, e.g. by reducing bone marrow blasts through therapy, would potentially affect transplant results. In particular the decision to treat patients before transplant or perform an upfront allogeneic transplantation can so far not be based on evidence. We did a registry search based in the MDS quality initiative conducted by EBMT to identify transplanted patients with MDS and sufficient data to calculate IPSS-R at diagnosis and before transplant. The search was limited to patients reveiving a first allogeneic stem cell transplantation in the period 2005 -2018. 1482 patients were identified. Median age at alloHCT was 59 (interquartile range 51-64) years, 60% were male. Donors were related in 36%, graft source was PBSC in 85% of cases. Conditioning was standard dose in 33% and reduced intensity in 67%. IPSS-R both at diagnosis and at transplant had a significant impact on OS and RFS after alloHCT. To investigate the effect of a change in IPSS-R between diagnosis and transplant we constructed 3 subgroups: stable IPSS-R, improved IPSS-R, worsened IPSS-R. A change in IPSS-R was noted in 77.5% of patients with prior chemotherapy, 72% with prior HMA and 59.8% of untreated patients. Univariate analysis showed no significant difference in OS or RFS in patients with stable IPSS-R compared to improved or worsened IPSS-R. In patients treated with chemotherapy before transplant OS and RFS was significantly worse with worsened IPSS-R, while this effect was not found in patient treated with hypomethylating agents (HMA) or untreated patients. The same analysis was performed regarding the difference in bone marrow blasts and the cytogenetics score: OS and RFS after transplant were significantly worse with increased blasts (p=0.04 and p=0.001) and a worsened cytogenetic score before transplant (both p&lt;0.001). While worsened IPSS-R, blast count or cytogenetic score had a negative impact on transplant outcome, the improvement of these parameters showed no positive effect on either OS or RFS in the total cohort or in the subgroups of untreated patients, after chemotherapy or after HMA treatment. In this retrospective analysis from a large cohort of patients with MDS we found that worsening of IPSS-R, blast count or cytogenetic score had a negative prognostic impact in chemotherapy-treated patients, while only worsened blast count and cytogenetics were significant negative factors in HMA-treated or untreated patients. Conversely we did not find a positive effect of improved IPSS-R, decreased blasts or improved cytogenetics in any of the subgroups of treated or untreated patients. Thus for MDS patients receiving an allogeneic transplantation our results provide no clear signal that prior therapy is able to improve transplant outcome. Disclosures Scheid: Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria; Takeda: Honoraria, Research Funding. Blaise:Jazz Pharmaceuticals: Honoraria. Chevallier:Incyte Corporation: Honoraria. Yakoub-Agha:Celgene: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria.

White Blood Cell Count Nadir and Duration of Aplasia Do Not Associate with Treatment Outcome in Adult Patients with Acute Myeloid Leukemia Undergoing Intensive Chemotherapy

<b><i>Introduction:</i></b> Adult patients with acute myeloid leukemia (AML) are usually treated with intensive chemotherapy, leading to prolonged bone marrow aplasia. It is usually assumed that a short duration of aplasia could be a surrogate marker of poor therapeutic efficacy in clearing bone marrow blasts, especially in older patients. No studies have evaluated the usefulness of such a surrogate marker in younger AML patients treated with intensive chemotherapy. <b><i>Materials and Methods:</i></b> In the present study, we retrospectively assessed the role of white blood cell (WBC) count nadir and duration of aplasia in 68 patients with AML treated with intensive chemotherapy and potentially candidate to stem cell transplantation. <b><i>Results:</i></b> The median (interquartile range) bone marrow aplasia was 25 days, and the mean WBC count nadir from chemotherapy start was at day +12, whereas the median neutrophil recovery occurred at day +24. No significant differences were found between responders and nonresponders for mean aplasia duration (25 vs. 26 days, <i>p</i> value = 0.76), mean WBC count nadir (12 vs. 12 days, <i>p</i> value = 0.86), and median neutrophil recovery (24 vs. 24, <i>p</i> value = 0.67). <b><i>Discussion:</i></b> The present study evaluated the potential prognostic role of WBC count nadir and duration of aplasia, demonstrating that they are not associated with treatment outcomes in adult patients with AML treated with intensive chemotherapy. Therefore, a short duration of aplasia seems not linked to poor therapeutic efficacy in clearing bone marrow blasts. Our findings, although needing validation in larger and more homogeneous cohorts, may offer helpful clues in the management of aplasia of AML patients.