Lenalidomide reexposure After Short Interruption In Del(5q) MDS Patients at Relapse of Transfusion Dependence

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2923-2923 ◽  
Author(s):  
Robert Marek Radkowski ◽  
Sabine Haase ◽  
Brigitte Schlegelberger ◽  
Gudrun Goehring ◽  
Stefanie Banisch ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Median Time ◽  
Chromosomal Abnormality ◽  
Myeloid Leukemia ◽  
Red Cell ◽  
Transfusion Independence ◽  
Free Interval ◽  
Red Cell Transfusion ◽  
Time To Relapse ◽  
Acute Myeloid

Abstract Abstract 2923 Introduction: Lenalidomide is effective in myelodysplastic syndroms (MDS) in patients with del(5q) chromosomal abnormality (List et al 2006). However, relapse of transfusion dependence occurs consistently and therapeutic measures at that moment are scarce. We report on our experience to achieve a second remission of transfusion dependence using lenalidomide after a variable period of lenalidomide treatment interruption. Methods: 5 patients with a del(5q) chromosomal abnormality (low- and intermediate-1-risk MDS according to IPSS) were treated within clinical trials, all transfusion-dependent with a median age of 67 years and with female prevalence. Mean MDS duration before start of lenalidomide therapy was 4.2 years. Patients were treated with doses of oral lenalidomide ranging from 5 mg every other day to 10 mg for 28 days of every 28 days cycle. All patients had a response to the initial lenalidomide treatment and achieved transfusion independence. All 5 patients relapsed and became red cell transfusion dependent, again. Median time to relapse was 24.2 months (13-55 months).The therapy was stopped and after a therapy-free interval of 7.2 months (2-13 months) we resumed lenalidomide therapy. The patients were treated with the initial lenalidomide dose. Results: 3 of 5 patients (60%) became transfusion independent, again. The median increase in hemoglobin from baseline to the maximum hemoglobin achieved was 4.4 g/dl. Patients are followed up and all of them are currently in ongoing transfusion independence with a median time of 16.3 months (11, 15, 23 months, respectively). The other two patients stayed transfusion dependent and lenalidomide was interrupted after 3 and 4 months, respectively. Both later progressed to higher MDS subtypes or acute myeloid leukemia. Responses seemed to be independent on age, time to relapse, interval to retreatment or doses of lenalidomide. Discussion: In low/int-1 IPSS del(5q) patients relapsing with red cell transfusion dependence during lenalidomide treatment, current algorithms recommend discontinuation of the drug. Our results suggest efficacy of lenalidomide in a significant portion of the patients when they are rechallenged with a standard dose after a therapy-free interval of 2 to 6 months. Second remissions might be as long lasting as, or exceeding, the initial one. We are unable to define predictive factors for second responses. Lack of further response may be an ominous prognostic sign and, in our experience, heralded progression to higher risk MDS subtypes or acute myeloid leukemia after a short time. Disclosures: Giagounidis: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Genetic Evolution of Cytogenetically Normal Acute Myeloid Leukemia (CN-AML) during Therapy and Relapse: An Exome Sequencing Study of 47 Cases

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 17-17
Author(s):  
Luise Hartmann ◽  
Sebastian Vosberg ◽  
Klaus H. Metzeler ◽  
Daniela Schumacher ◽  
Friederike Pastore ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Disease Progression ◽  
Exome Sequencing ◽  
Median Time ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Genetic Evolution ◽  
Course Of Disease ◽  
Time To Relapse ◽  
Acute Myeloid

Abstract The evolution of acute myeloid leukemia (AML) has been previously described either in studies of large patient cohorts with focus on only a restricted number of AML-associated genes or in smaller series of relapsed patients studied by genome-wide techniques. We set out to comprehensively characterize the genetic evolution in a large AML cohort in order to understand molecular mechanisms of relapse and therapy-resistance. We performed exome-sequencing of matched bone marrow or peripheral blood samples taken at diagnosis, complete remission and relapse from 47 patients with cytogenetically normal AML (CN-AML). Samples were collected within the German Cancer Consortium (DKTK) at the partner sites in Berlin and Munich. The median age at diagnosis was 65y (range: 21-89y). FLT3 internal tandem duplication (ITD) and NPM1 mutation status at diagnosis was available for all but one patient (FLT3-ITD-/NPM1-, n=5; FLT3-ITD+/NPM1-, n=9; FLT3-ITD-/NPM1+, n=16; FLT3-ITD+/NPM1+, n=16). On average, 96% of the target sequence was covered at least 10-fold (minimum coverage defined for variant calling). The following criteria were applied for identification of somatic mutations: Variant allele frequency (VAF) ³20% either at diagnosis or at relapse and VAF<5% at remission. We filtered for mutations with translational consequences, excluded known error-prone genes and dismissed common germline polymorphisms (dbSNP 138; MAF³1%). Thereby, we identified a total of 777 genes to be somatically mutated, of which 104 were recurrently affected. Mutation frequencies of 18 genes found mutated both in our cohort and in 86 CN-AML patients reported by The Cancer Genome Atlas (TCGA, NEJM 2013) are shown in Figure 1 A. Seven genes were recurrently altered only at diagnosis (e.g. CBL) and 16 genes were recurrently altered only at relapse in our cohort (e.g. KDM6A, SF3B1 and SRSF2). At diagnosis, the number of somatic mutations per patient varied between 5 and 34 (median: 17). At relapse, the number of mutations ranged from 2 to 57 (median: 17). Mutations in several AML-associated genes (e.g. DNMT3A, RUNX1, IDH1 and IDH2) showed similar VAFs at diagnosis and relapse in the vast majority of cases. In contrast, WT1 mutations were gained at relapse in 4/6 (67%) patients and FLT3 point mutations were below 5% VAF at relapse in 7/12 (58%) patients initially positive for these variants. In total, 92 mutations present at diagnosis were lost at relapse (VAF <5%) while 116 mutations were acquired during disease progression. Based on cytogenetics and copy number alteration (CNA) analysis of exome data, we detected partial or complete gain/loss of chromosomes. Five patients (11%) acquired chromosomal alterations during disease progression. Trisomy 8 was the only recurrent chromosomal abnormality gained in 3 patients (6%) at relapse. To detect pre-leukemic lesions, we evaluated our exome data for the persistence of mutations in 40 AML-associated driver genes during remission. We limited our analysis to mutations previously reported as confirmed somatic (COSMIC annotation) to avoid confounding with private germline variants. Strikingly, 25/47 (53%) of patients carried non-silent mutations in these genes with VAF>5% (median: 31%, range: 9-75%) at remission (30 mutations in total). In contrast, other mutations (e.g. in FLT3 or NRAS) found in these patients could not be detected at remission, consistent with therapy response. Based on VAF, 23/30 (77%) persistent mutations showed a dynamic pattern over the course of disease with a relative change of >20%, likely due to partial eradication/expansion of leukemic or pre-leukemic clones. Persistent mutations in DNMT3A, TET2, RUNX1 and IDH2 were observed in 28%, 11%, 6% and 4% of patients in our cohort, respectively (Figure 1 B). Among patients with DNMT3A mutation at diagnosis, those with persistent mutations tended to relapse earlier (n=13; median time to relapse 270 days; range: 81-586) than patients without detectable DNMT3A mutations at remission (n=7; median time to relapse 508 days; range: 235-1697; p=0.111). Our findings provide insights into the genetic evolution during the course of disease in a large cohort of relapsed CN-AML. Information about the dynamics of genetic lesions (e.g. persistent or relapse-specific mutations) may have prognostic significance and allow for tailored approaches to treat or to prevent relapse of AML. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Phase 3 VERONA study of venetoclax with azacitidine to assess change in complete remission and overall survival in treatment-naïve higher-risk myelodysplastic syndromes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS7054-TPS7054
Author(s):  
Amer Methqal Zeidan ◽  
Jacqueline Suen Garcia ◽  
Pierre Fenaux ◽  
Uwe Platzbecker ◽  
Yasushi Miyazaki ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Hypomethylating Agents ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Transfusion Independence ◽  
Treatment Naïve ◽  
The U.S ◽  
Acute Myeloid

TPS7054 Background: Patients with higher-risk myelodysplastic syndromes (HR-MDS) experience peripheral cytopenias, disease progression to acute myeloid leukemia, and high mortality with expected median overall survival of less than 2 years. Allogeneic hematopoietic cell transplantation (allo-HCT) is the only potentially curative treatment. Patients ineligible for transplantation are treated with hypomethylating agents such as azacitidine (Aza), which is not curative and provides limited improvement in clinical benefit. Venetoclax (Ven) is a selective, potent, oral B-cell lymphoma-2 (BCL-2) inhibitor that is approved in the U.S. in combination with hypomethylating agents for treating older or co-morbid patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Ven is approved in the U.S. as first-line treatment for chronic lymphocytic leukemia or small lymphocytic lymphoma. For patients with treatment-naïve HR-MDS, Ven + Aza demonstrated manageable safety and a combined complete remission (CR)/marrow CR (mCR) rate of 79% in a single arm phase 1b study (NCT02942290). To confirm these benefits, the VERONA study, a randomized, double-blind, phase 3 study (NCT04401748) of patients with treatment-naïve HR-MDS, will assess the safety and efficacy of Ven combined with Aza including CR rate and overall survival. Methods: Patients (≥18 years) with newly diagnosed HR-MDS per WHO 2016 classification with = 20% bone marrow blasts per marrow biopsy/aspirate at screening will be enrolled at ̃200 sites globally (̃500 patients). Patients must have intermediate risk or higher IPSS-R (score > 3), ECOG ≤2, and be hematopoietic stem cell transplant (HSCT) eligible without any pre-arranged donor, or HSCT ineligible without a plan for HSCT at Study Day 1. De novo patients without prior hypomethylating agents, chemotherapy for MDS, or allogenic stem cell transplantation are eligible. Patients will be randomized 1:1 to receive placebo or Ven 400 mg oral tablet once daily on Days 1-14, both in combination with Aza 75 mg/m2 (intravenous or subcutaneous) on Days 7-0-0 or Days 5-2-2 per 28-days. Patients will receive study treatment until disease progression, unacceptable toxicity, HCT, withdrawal of consent, or discontinuation. The primary endpoints are CR rate (as adjudicated by investigator) per IWG 2006 criteria and overall survival. Secondary outcomes are red blood cell transfusion independence, platelet transfusion independence, change in fatigue as measured by Patient-Reported Outcomes Measurement Information System (PROMIS)-fatigue SF 7a scale score, time to deterioration in physical functioning domain of EORTC QLC-C30 scale, overall response (CR + partial response), and modified overall response (CR + mCR + partial response). Exploratory objectives are predictive biomarkers and pharmacokinetics. Clinical trial information: NCT04401748.

scholarly journals Transfusion independence and survival in patients with acute myeloid leukemia treated with 5-azacytidine

Haematologica ◽  
2012 ◽  
Vol 97 (12) ◽  
pp. 1929-1931 ◽  
Author(s):  
M. Gavillet ◽  
J. Noetzli ◽  
S. Blum ◽  
M. A. Duchosal ◽  
O. Spertini ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Transfusion Independence ◽  
Acute Myeloid

Unrelated cord blood transplantation for adult patients with de novo acute myeloid leukemia

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 489-491 ◽  
Author(s):  
Jun Ooi ◽  
Tohru Iseki ◽  
Satoshi Takahashi ◽  
Akira Tomonari ◽  
Kashiya Takasugi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cord Blood ◽  
Median Time ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Cord Blood Transplantation ◽  
Adult Patients ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Acute Myeloid

Abstract We report the results of unrelated cord blood transplantation (CBT) for 18 adult patients with de novo acute myeloid leukemia (AML). The median age was 43 years, the median weight was 55.2 kg, and the median number of cryopreserved nucleated cells was 2.51 × 107/kg. Seventeen patients had myeloid reconstitution and the median time to more than 0.5 × 109/L absolute neutrophil count was 23 days. A self-sustained platelet count more than 50 × 109/L was achieved in 16 patients at a median time of 49 days. Acute graft-versus-host disease (GVHD) above grade II occurred in 11 of 17 evaluable patients and chronic GVHD occurred in 14 of 17 evaluable patients. Fourteen patients are alive and free of disease at between 185 and 1332 days after transplantation. The probability of disease-free survival at 2 years was 76.6%. These results suggest that adult AML patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT.

Translocation (13;17)(q14;q25) as a novel chromosomal abnormality in acute myeloid leukemia-M4

2006 ◽  
Vol 30 (7) ◽  
pp. 903-905 ◽  
Author(s):  
Nihan Turhan ◽  
Nüket Yürür-Kutlay ◽  
Pervin Topcuoglu ◽  
Müyesser Saykı ◽  
Meltem Yüksel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Chromosomal Abnormality ◽  
Myeloid Leukemia ◽  
Acute Myeloid

Clinical Useful Prognostic Index for Adult Patients with Acute Myeloid Leukemia in First Relapse.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2011-2011
Author(s):  
Dimitri A. Breems ◽  
Wim L.J. Van Putten ◽  
Bob Lowenberg
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Prognostic Index ◽  
Free Interval ◽  
First Relapse ◽  
One Year ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract The treatment of acute myeloid leukemia (AML) in first relapse is associated with unsatisfactory rates of complete responses that are usually short lived. Previously proposed prognostic classification methods serving therapeutic decisions and evaluation of investigational treatment strategies at relapse of AML have been based on the duration of the relapse free interval and have largely neglected the influence of other known prognostic factors. Here we present an improved clinically useful prognostic index. This index has been developed from a multivariate analysis of 667 AML patients in first relapse among 1540 newly diagnosed non-M3 AML patients of age 15 to 60 years entered into three successive HOVON/SAKK Collaborative Group trials. The score, which has a range of 0 to 14 points, uses four relevant parameters. The parameters are: length of relapse free interval after first complete remission (more than 18 months: 0 points; 7 to 18 months: 3 points; 6 months or less: 5 points), cytogenetics at diagnosis (t(16;16) or inv(16): 0 points; t(8;21): 3 points; other cytogenetics: 5 points), age at relapse (35 years or younger: 0 points; 36 to 45 years: 1 point; older than 45 years: 2 points) and whether or not a previous stem cell transplantation (SCT) has been undertaken in first complete remission (no SCT: 0 points; previous SCT: 2 points). These points were assigned following estimations of the relative values of each of these factors contributing to outcome. Ultimately, three risk groups were defined: a favorable prognostic group A (0 to 6 points; overall survival of 70% at one year and 46% at five years), an intermediate risk group B (7 to 9 points; overall survival of 49% at one year and 18% at five years), and an unfavorable risk group C (10 to 14 points; overall survival of 16% at one year and 4% at five years). Thus, four commonly applied clinical parameters may identify among patients with AML in first relapse those for salvage or investigational therapy.

Myelodysplastic Syndrome Patients Obtaining a Cytogenetic Response to Outpatient Decitabine Experience Improved Hematological Responses and Longer Survival: Additional Analyses From the ADOPT Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3817-3817 ◽  
Author(s):  
Stuart L. Goldberg ◽  
David P Steensma
Keyword(s):  
High Risk ◽  
Median Time ◽  
Platelet Transfusion ◽  
Cytogenetic Response ◽  
Post Treatment ◽  
Red Cell ◽  
Transfusion Independence ◽  
Hematological Response ◽  
Red Cell Transfusion ◽  
Secondary Mds

Abstract Abstract 3817 Poster Board III-753 Background The multi-center ADOPT trial (J Clin Oncol 2009; 27:3942) demonstrated that decitabine (Dacogen), a cytidine analog with hypomethylating and direct cytotoxic properties, when administered to MDS patients with IPSS '0.5 on an outpatient schedule of 20 mg/m2 IV infusion 5 days per month resulted in an overall improvement rate of 51%, including 32% complete responses (CR+mCR), using the International Working Group 2006 criteria. The impact of obtaining a cytogenetic response to decitabine therapy on subsequent hematological parameters or survival is the focus of this analysis. Study Design/Methods 99 patients with de novo or secondary MDS were enrolled on the ADOPT trial. 49 patients had abnormal cytogenetics at baseline. 33 patients underwent at least one successful post-treatment karyotypic analysis and were therefore evaluable for cytogenetic response. Data analysis utilized student t-tests and comparisons of proportions. Results 17/33 evaluable patients (52%) achieved a cytogenetic response, with 11 complete responses and 6 partial responses (i.e., >50% reduction in abnormal metaphases). Responses were noted among patients in all IPSS cytogenetic risk categories: low risk cytogenetics 3/3 (100%), intermediate risk cytogenetic 5/8 (62%), and high risk cytogenetic (43%). Cytogenetic responses by abnormality included: -Y (3/3), del 5q (1/7) 1, del 20q (1/2), complex (6/14), chromosome 7 abnormalities (6/14), +8 (5/6), and others (3/7). Baseline characteristics were similar among cytogenetic responders and non-responders: mean age 72.2 vs 68.6 years (p=0.30), males 94 vs 63% (p=0.07), secondary MDS 24 vs 13% (p=0.72), high risk IPSS 35 vs 63% (p=0.21), int-2+high risk IPSS 59 vs 85% (p=0.20), blasts <10% 59 vs 31% (p=0.21), red cell transfusion dependent 41 vs 69% (p=0.21) and platelet transfusion dependent 6 vs 19% (p=0.54). The median time to cytogenetic response was 2.3 months, coinciding with the first post-treatment marrow sampling timing. Of the 17 cytogenetic responders, 13 (76%) had a clinical hematological responses (10 CR and 3 mCR) which was significantly higher (p=0.003) than the 3 of 16 evaluable patients (18%) not experiencing a cytogenetic response. Among cytogenetic responders the duration of the hematological response (451 days, 95% CI 143, NE) also was greater than the duration of hematological response among cytogenetic non-responders (219 days, 95% CI 184, NE). 71% (12/17) of cytogenetic responders were red cell transfusion independent on study by IWG criteria compared to 44% (7/16) non-cytogenetic responders (p=0.22). Significantly more cytogenetic responders achieved prolonged red cell transfusion independence lasting at least 24 weeks (10/17; 59%) compared to cytogenetic non-responders (3/16; 19%) (p=0.04). 88% (15/17) of cytogenetic responders were platelet transfusion independent during the study compared to 75% (12/16) non-cytogenetic responders (p=0.61). Higher rates of prolonged platelet transfusion independence lasting at least 24 weeks were achieved among 82% (14/17) cytogenetic responders versus only 38% (6/16) cytogenetic non-responders (p=0.03). Achieving a cytogenetic response correlated with improved survival. Cytogenetic responders had a median survival of 627 days (95% CI 420,760) versus 318 days (95% CI 265, 447) for cytogenetic non-responders. Conclusions Outpatient administration of decitabine (20mg/m2 IV 5 days per month) resulted in cytogenetic responses in 52% of patients with MDS with baseline cytogenetic abnormalities, with a median time to response of 2.3 months. Patients achieving a cytogenetic response had higher rates of hematological responses, longer durations of transfusion independence, and a doubling of projected survival. This analysis suggests that a deeper early response documented by cytogenetics with decitabine correlates with improved long term outcomes, and supports early cytogenetic testing to predict hematological response. Disclosures: Goldberg: Eisai, Inc.: Research Funding.

Combination of Mitoxantrone,Ara-C and Homoharringtonine In Treatment of Refractory and Relapsed Acute Myeloid Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4294-4294
Author(s):  
Jianda Hu ◽  
Tingbo Liu ◽  
Chunxia Cai ◽  
Xinji Chen ◽  
Buyuan Chen
Keyword(s):  
Drug Resistance ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Abstract Abstract 4294 Advances in effective chemotherapy have improved clinical outcomes in acute leukemia in recent years. 5-year survival rate approaches 50–60% for acute myeloid leukemia (AML). However, the prognosis remains poor for patients who are relapsed or refractory to first-line therapy. Drug resistance and early disease recurrence are major contributing factors in the limited survival of patients with AML. The strategy for treating these patients is through reinduction chemotherapy followed by allogeneic stem cell transplantation. New combinations of different agents were employed in refractory patients to overcome drug resistance. The current study is to evaluate the efficacy of a MAH regimen comprising Mitoxantrone,Ara-C and Homoharringtonine in refractory or relapsed AML. 37 patients aged 14–65 years with refractory or relapsed AML (15 refractory AML patients, 22 relapsed AML patients) were treated with the MAH regimen(Mitoxantrone 10mg qd, iv.gtt, for 2□‘3 days;Ara-C 100mg bid, iv.gtt, for 5□‘7 days; Homoharringtonine 4mg qd iv.gtt, for 5□‘7 days). Chemotherapy duration lasted for 5 or 7days depended on bone marrow cellurarity. 15 (40.5%)and 1 (2.7%) patients achieved complete remission (CR) and partial remission (PR) respectively. The overall response rate was 43.2%. There was no relation between remission duration and previous chemotherapy. All patients who achieved CR received a consolidation and intensification therapy. The median overall survival (OS) for all patients was 97 days (range 18–487 d). For the patients who were in CR or PR,the median relapse-free survival(RFS) was 147 days(range 4 to 341 d). All patients experienced profound myelosuppression. The most common observed side effect of the regimen was infection because of grade ‡W neutropenia, which could be observed in 33 patients(89.1%). 4 patients died in aplasia due to severe infection and brain hemorrhage. In patients achieving remission, the median time to reach absolute neutrophil count (ANC) more than 0.5×109/l was (16.0±6.4)d. Platelet levels of more than 20×109/l were achieved in a median time of (12.7±6.2)d. Nonhematological side effects, consisting mainly of gastrointestinal toxicity(21/37,56.8%) and transient liver ALT and AST increase (4/37), were generally mild to moderate and tolerated. To a conclusion, MAH regimen can be employed in treatment of the refractory or relapsed AML patients who were not responded to other regimen. It is effective and is good tolerant.It could provide some refractory patients the chance to receive hematopoietic stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

Treatment with FLAG followed by second allogeneic stem cell transplant for relapsed acute myeloid leukemia and myelodysplastic syndrome.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18503-e18503
Author(s):  
Brian Pham ◽  
Rasmus Hoeg ◽  
Nisha Hariharan ◽  
Kathyryn Alvarez ◽  
Aaron Seth Rosenberg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Time To Relapse ◽  
Acute Myeloid

e18503 Background: There is no standard treatment for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) relapsing after allogeneic stem cell transplant (SCT). Options include combination chemotherapy, withdrawal of immunosuppression, donor lymphocyte infusion (DLI), and second SCT. Previous studies have used fludarabine, cytarabine, and granulocyte colony stimulating factor (FLAG) or second SCT separately for salvage therapy. Our institution uses FLAG followed by SCT from the same donor (FLAG/SCT) in this setting. We report a retrospective study of FLAG/SCT in MDS and AML patients relapsed after SCT. Methods: Patients who received FLAG/SCT for treatment of relapsed AML or MDS between 2009 and 2018 were identified using the bone marrow transplant database at University of California Davis. Their baseline characteristics and outcomes were determined using the electronic medical record. Descriptive statistics and Kaplan-Meier survival analysis were used to describe patients, rates of graft-versus-host disease (GvHD) and estimate survival times. Results: Nineteen patients received FLAG/SCT for AML (n=18) and MDS (n=1). Median time to relapse from first SCT was 145 days (range 41 to 960 days). Prior to FLAG/SCT, 17 patients had medullary relapse (median bone marrow blasts 27%; range 7-85%). Two patients had extramedullary relapse. Eighteen (94.7%) patients achieved complete remission (CR) after FLAG/SCT. Median follow-up time was 354 days from the first day of FLAG/SCT (range 7 to 2144 days). Six patients (31.6%) relapsed with median time to relapse of 334 days (range 78 to 679 days) after treatment. Overall survival at 2 years was 52.5%. Causes of death were relapsed AML (n=4; 21.1%), infection (n=4; 21.1%) complications of GvHD (n=3,15.8 %), and brain herniation (n=1, 5.3%). Acute GvHD grade I-IV and new onset chronic GvHD occurred in thirteen (68.4%) and eight patients (42.1%), respectively. Conclusions: FLAG/SCT for AML and MDS relapsing after SCT resulted in a high remission rate. The overall survival of over two years suggests that the second SCT augmented the graft versus leukemia effect. The GvHD rate increased after second SCT, but the rate and severity were manageable. FLAG/ SCT is a reasonable option for relapsed AML and MDS after SCT.

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