scholarly journals Haplotype mismatched transplantation using high doses of peripheral blood CD34+ cells together with stratified conditioning regimens for high-risk adult acute myeloid leukemia patients: a pilot study in a single Korean institution

2005 ◽  
Vol 35 (10) ◽  
pp. 959-964 ◽  
Author(s):  
H-J Kim ◽  
W-S Min ◽  
Y-J Kim ◽  
D-W Kim ◽  
J-W Lee ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Pilot Study ◽  
High Risk ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells ◽  
Conditioning Regimens ◽  
High Doses ◽  
Acute Myeloid

Azacitidine With Or Without Entinostat For The Treatment Of Therapy-Related Myeloid Neoplasm: Further Results Of The E1905 North American Leukemia Intergroup Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2777-2777
Author(s):  
Thomas Prebet ◽  
Zhuoxin Sun ◽  
Rhett Ketterling ◽  
Peter L. Greenberg ◽  
Amer M. Zeidan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
North American ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Response Rates ◽  
High Response ◽  
Myeloid Neoplasm ◽  
Acute Myeloid

Abstract Background Therapy-related myeloid neoplasm (tMN) includes t-myelodysplasia (tMDS) and t-acute myeloid leukemia (tAML) and are serious late effects of the treatment of cancer. Prognosis of tMN is poor, related to the increased frequency of adverse cytogenetics and other clinical features which predict poor response to conventional treatment. Over the last years, azacitidine (AZA) has become the standard of treatment for high risk MDS (Silverman, JCO 2002; Fenaux, Lancet Oncol 2009) and has shown efficacy in AML. AZA represents an interesting option for patients with tMN considering its safety profile and its efficacy in poor prognosis subgroups of apparently de novo MDS patients including those with monosomy 7. Most prospective trials of AZA have excluded patients with tMN. Most tMN data are retrospective or registry studies (Bally, Leuk Res 2013). This abstract presents the results of 47 t-MN patients prospectively enrolled as a specific cohort in the E1905 study. Methods E1905 study is a randomized phase 2 study from the North American Leukemia Intergroup (NCT00313586, Prebet , ASH 2010) testing 10 days of AZA (50mg/m2/d s.c.) vs. 10 days of AZA + the histone deacetylase inhibitor entinostat (4 mg/m2/d PO days 3 and day 10). 6 cycles of treatment were planned; responding patients could receive up to 24 cycles. MDS, CMML, and AML with myelodysplasia-related changes were included. Patients with tMN were subsequently accrued as a separate cohort after amendment of the protocol. Response was assessed using IWG 2000 criteria (Cheson et al, Blood 2000); the primary endpoint of the overall trial was achievement of a normal hemogram in 25% of treated patients in either treatment arm. Results A total of 47 patients were included. Median age was 70 years (39y-83y), 45% male, and 94% of patients had ECOG PS 0-1. 29 patients could be subclassified as t-MDS and 18 as t-AML. At inclusion, median peripheral blood counts were: neutrophils 1.0 G/l, Platelets 35 G/L, Hemoglobin 9.2 g/l, peripheral blood blasts 0%, marrow blasts 14.0%. 68% of patients were RBC transfusion dependent and 40% platelet transfusion dependent. As expected, the cytogenetic evaluation showed a high frequency of unfavorable risk cytogenetics (74%) as compared to normal or intermediate risk cytogenetics (26%). Baseline characteristics were not statistically different between the 2 arms. 24 patients were treated with AZA monotherapy and 23 with AZA+entinostat. The median number of administered cycles was 4 and was significantly higher in patients treated with AZA monotherapy (6 cycles vs.3 cycles, p=0.008). 8 patients in the combination arm and 1 patient in the AZA monotherapy arm died of infection or hemorrhage before cycle 3. In an intent to treat analysis, overall response rates (CR, PR, or trilineage Hematologic improvement) were 11/24 (46%) in AZA monotherapy (95% CI 26 – 67%) and 4/23 (17%) in the combination arm (95% CI 5 – 39%, p=0.06 comparing the two arms). Median overall survival in the two arms were 12.8 months and 5.7 months (p=0.008). Conclusions In this group of very high risk patients with therapy-related myeloid neoplasms, the use of the novel 50 * 10 schedule of azacitidine monotherapy appears effective, with response rates comparable to those for patients with de novo MDS/AML treated on the same protocol (74 pts, 40% with unfavorable cytogenetics, ORR=32%, median OS=18 months). Because there are no prospective data examining the approved dose schedule of AZA (75 mg/m2/day * 7 days), it is not clear if this surprisingly high response rate derives from the current extended schedule of lower dose AZA, or would be true with standard dose AZA as well. This high response may enable many of these patients to proceed to allogeneic stem cell transplant. Entinostat combined with azacitidine at the dose and schedule applied in E1905 does not appear to be effective and tolerable as compared to azacitidine alone. Disclosures: Prebet: CELGENE: Honoraria. Off Label Use: Use of azacitidine in acute myeloid leukemia. Gore:CELGENE: Equity Ownership, Research Funding.

scholarly journals Outpatient intensive induction chemotherapy for acute myeloid leukemia and high-risk myelodysplastic syndrome

2020 ◽  
Vol 4 (4) ◽  
pp. 611-616
Author(s):  
Frances Linzee Mabrey ◽  
Kelda M. Gardner ◽  
Kathleen Shannon Dorcy ◽  
Andrea Perdue ◽  
Heather A. Smith ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Pilot Study ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Outpatient Setting ◽  
Successful Implementation ◽  
Chemotherapy Administration ◽  
Acute Myeloid

Abstract To improve patient quality of life and reduce health care costs, many conditions formerly thought to require inpatient care are now treated in the outpatient setting. Outpatient induction chemotherapy for acute myeloid leukemia (AML) may confer similar benefits. This possibility prompted a pilot study to explore the safety and feasibility of intensive outpatient initial or salvage induction chemotherapy administration for adults with AML and high-risk myelodysplastic syndrome (MDS). Patients with no significant organ dysfunction and a treatment-related mortality (TRM) score corresponding to a day 28 mortality rate of <5% to 10% were eligible for study. Patients were treated as outpatients with daily evaluation by providers and only admitted to the hospital if mandated by complications. Twenty patients were consented, and 17 were treated. Eight patients received initial induction chemotherapy and 9 received salvage induction chemotherapy. Fourteen patients completed induction chemotherapy administration in the outpatient setting (82.4%; exact 95% confidence interval [CI], 55.8-95.3). Three patients were admitted during the course of chemotherapy administration, 2 for neutropenic fever and 1 for grade 3 mucositis. No patients died within 14 days of the initiation of induction chemotherapy (exact 95% CI, 0-22.9). Results of this pilot study suggest it is feasible to complete outpatient induction chemotherapy in select patients with AML and high-risk MDS. A team including nurses, social workers, medical providers, and pharmacists was key to the successful implementation of outpatient induction.

scholarly journals Comparison of FLU-BU12 Conditioning with the Standard BU-CY Myeloablative Regimen in High-Risk Pediatric ACUTE Myeloid Leukemia Patients Undergoing Allogeneic STEM Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-31
Author(s):  
Olesia V Paina ◽  
Zhemal Zarifovna Rakhmanova ◽  
Polina Valerievna Kozhokar ◽  
Anastasia S Frolova ◽  
Liubov A. Tsvetkova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Conditioning Regimens ◽  
Acute Myeloid

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for high-risk acute myeloid leukemia (AML).The preparative regimen consisting of busulfan and cyclophosphamide (BuCy) is considered as one of the classical myeloablative conditioning regimens (MAC); however, it is associated with significant early and long-term toxicities, leading to a high rate of transplant-related mortality (TRM). P urpose: To compare toxicities and outcomes of BuCy and FluBu12 conditioning in the pediatric population. Methods: We retrospectively analyzed 71 pediatric high-risk AML patients in CR1/2 (n=51, 71,8%) and R/R disease (n=20, 28,2%) received allo-HSCT from MSD (n=16, 22,5%), MUD (n=43, 60,6%) and Haplo donor (n=12, 16,9%). BuCy and FluBu conditioning regimens were used in 47 (66,2%) and 24 (33,8%) patients respectively. Median age was 6 years (0-17). GVHD prophylaxis was PTCy±CNI±m-TOR inhibitor in 32 (45%) or ATG±CNI in 39 (55%) patients. The primary end points were TRM, relapse-free survival (RFS), graft-versus-host disease (GVHD) free, relapse free survival (GRFS) and overall survival (OS). Secondary end points included neutrophil engraftment, sinusoidal obstruction syndrome (SOS), acute and chronic GVHD. Patient were censored at the time of death or last follow-up. Probabilities of OS, RFS and GRFS were estimated using Kaplan-Meier curves. TRM was defined as any death that occurred in the absence of disease relapse; relapse was a competing risk for this event. Results: Engraftment rate was 91% and 87,5% in patients received BuCy and FluBu, respectively (p=0,4). There was a trend to lower day 100 TRM after FluBu (4,1% vs 14,9% after BuCy, p=0,07). Overall survival at 2 years did not differ as well (BuCy 48,9%, FluBu 56%, p=0,5). BuCy showed borderline higher RFS at 2 years (70,2% vs 52%, p=0,06). The composite endpoint GRFS did not differ between two study cohorts being 31,8% and 29,2% at 2 years for BuCy and FluBu (p=0,7). We observed a tendency towards a higher incidence of III0-IV0 aGVHD and cGVHD following BuCy when compared with FluBu: 57,1% vs 41% (p=0,06) and 46,5% vs 28,5% respectively (p=0,2). No significant differences were found between the BuCy and FluBu groups in risk of SOS (6% and 8%, respectively). Conclusions: The optimal conditioning regimen for children with AML is still a matter of debate. Our results suggest that FluBu represents a valid myeloablative regimen, able to provide lower TRM, aGVHD and cGVHD. This conditioning might become an alternative approach in patients with a high risk of severe post-transplant complications. Disclosures No relevant conflicts of interest to declare.

Nanocytometer for smart analysis of peripheral blood and acute myeloid leukemia: a pilot study

Nano Letters ◽  
2020 ◽  
Vol 20 (9) ◽  
pp. 6572-6581
Author(s):  
Julian Schütt ◽  
Diana Isabel Sandoval Bojorquez ◽  
Elisabetta Avitabile ◽  
Eduardo Sergio Oliveros Mata ◽  
Gleb Milyukov ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Pilot Study ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Acute Myeloid

Phenotypic Aberrations of Myeloid CD34+ Cells in Patients with Myelodysplastic Syndrome (MDS): Clinical Significance and Correlation with Cytogenetics Abnormalities.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2374-2374
Author(s):  
Dolores Subira ◽  
Patricia Font ◽  
Eva Arranz ◽  
Ramiro B Soraya ◽  
Susana Castanon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Fish Analysis ◽  
Aberrant Expression ◽  
Number Of Patients ◽  
Cd34 Cells ◽  
Design And Methods ◽  
Acute Myeloid

Abstract Expression of abnormal markers in myeloid CD34+ cells of patients with MDS is common, but few immunophenotypic data have been compiled so far. Based on the statement that CD7 and TdT are markers associated with a bad prognosis in acute myeloid leukemia, we intended to describe the incidence of their aberrant expression in CD34+ cells and its role helping to establish the diagnosis of MDS. OBJECTIVES: To explore the aberrant expression of TdT and CD7 in myeloid CD34+ cells of MDS patients and to describe their possible correlation with cytogenetic features. DESIGN AND METHODS: Bone marrow specimens from 45 patients with MDS were included in this study (17 RA, 12 RARS, 5 CMML, 9 RAEB, 2 RAEB-t). In addition, we analyzed 28 samples of bone marrow from patients with cytopenias, but no diagnosis of MDS, as a cohort control. Immunophenotyping was performed with the following combination of monoclonal antibodies: TdT FITC / CD7 PE/ CD34 PCy-5. A case was regarded as positive for any of these markers when their expression was described in at least, 25% of myeloid CD34+ cells. Besides, adequate cytogenetic data and FISH analysis of chromosomes 5, 7 and 8 were obtained from 42 out of the 45 MDS samples. RESULTS: The percentage of CD34+ myeloid cells in MDS samples was fewer than 2% in 25 cases, ranged from 2–5% in 6 cases and was equal or greater than 5% in 14 cases. Aberrant expression of CD7 and/or TdT was observed in 28 cases: 20 were positive for CD7, 5 cases were positive for TdT and co-expression of both antigens was described in 3 cases. Prevalence of these abnormal markers was much higher in patients with MDS (28/45; 62%) than in the cohort control (2/28; 7%) . Besides, we identified at least one abnormal marker in 14 of the 16 patients with high risk MDS (9 RAEB, 5 CMML, 2 RAEB.t). According to the IPSS, karyotypes were divided into subgroups of favorable, intermediate or unfavorable, being classified 29 patients with favorable karyotypes and 13 patients with no favorable cytogenetics. In the first group, the abnormal expression of CD7 and/or TdT was detected in 13/29 patients (44.8%) and in 10/13 patients in the non-favourable group (76.9%). CONCLUSIONS: CD7 and/or TdT expression in myeloid CD34 + cells may be helpful in establishing the diagnosis of MDS. Prevalence of these aberrancies seems to be higher in cases with no favorable karyotypes, but a larger number of patients will be required to state significant differences. Possible correlation between high risk MDS patients and immunophenotypic aberrancies suggests the convenience of following the outcome of those low risk MDS patients who have expression of any of these abnormal markers.

5–azacitidine Treatment of Imminent Relapse Defined by Decreasing Donor CD34+ Progenitor Subset Chimerism in Patients with CD34+ High-Risk Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML) after Allogeneic Stem Cell Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2143-2143 ◽  
Author(s):  
Uwe Platzbecker ◽  
Joergen Radke ◽  
Alexander Kiani ◽  
Malte Bonin ◽  
Eray Goekkurt ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Donor Chimerism ◽  
Allogeneic Pbsct ◽  
Cd34 Cells ◽  
Acute Myeloid

Abstract Besides graft versus host disease (GVHD), disease relapse is one of the major challenges in the care of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic peripheral blood stem cell transplantation (PBSCT). However, we and others have shown that relapse can be predicted in case of CD34-expression on the malignant clone by a sensitive chimerism analysis in sorted CD34+ peripheral blood cells. If the percentage of donor cells in this compartment drops below 80%, leukemia relapse is inevitable within 4–8 weeks in the absence of clinical interventions like immediate cessation of immunosuppressive drugs or the administration of donor lymphocyte infusions. However, both approaches often result in clinically significant GVHD. Therefore, new strategies are warranted in order to treat imminent relapse in MDS or AML patients. We report results of an ongoing phase II clinical trial evaluating the efficacy of 5-azacitidine (5-aza) to prevent hematological relapse in patients with CD34+ AML or MDS and a decreasing CD34-donor chimerism after allogeneic PBSCT. Therefore, a total of 23 patients with CD34+ MDS (n=3) or AML (n=20) were prospectively screened on day 56, 84, 112, 140, 184, 365 and at later time points after PBSCT for a decreasing chimerism of donor CD34+ cells in the peripheral blood. In case of imminent relapse, defined as a drop of donor CD34+ cells below 80%, 5-aza was given at a dose of 75mg/m2/d s.c. day 1–7. A total of 4 cycles every 28 days were allowed in the absence of hematological relapse or toxicity. A median of 226 days after PBSCT, 9 out of 23 patients screened entered the treatment phase of the study with a median of 31% (range 0–53%) CD34+ donors cells in the peripheral blood (PB). However, a complete overall PB donor chimerism and less than 5% marrow blasts were documented in all patients before 5-aza treatment. Reversible neutropenia and thrombocytopenia grade 3/4 occurred in 50% of the patients. Only three patients still had immunosuppression prior 5-aza, which in two of them was slowly tapered during the period of 5-aza administration. With a median follow-up of 186 days after starting 5-aza all nine patients are eligible for response evaluation. Of these, CD34-chimerism was reverted to complete donor type (>90%) in 6 (66%) patients. Two patients showed a further decrease of donor CD34+ cells and relapsed shortly after having completed the 1st or the 4th cycle of 5-aza, respectively. One patient showed an increase of CD34-chimerism after two cycles, however, died from non-relapse mortality. No hematological relapse occurred in the responders and in the screening cohort without decreasing CD34+ chimerism. Two patients (one without immunosuppression) developed limited cGVHD during 5-aza treatment. Preemptive treatment of minimal residual disease defined by decreasing donor CD34+ subset chimerism with 5-aza seems to be a potent strategy to prevent hematological relapse of CD34+ myeloid malignancies after allogeneic PBSCT.

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