scholarly journals Chronic myelomonocytic leukemia “myelodysplastic type’’ in transformation to acute myeloid leukemia – diagnostic and therapeutic options: case report and literature review / Leucemie mielomonocitară cronică forma mielodisplazică în transformare spre leucemie acută mieloidă – diagnostic și opțiuni terapeutice: prezentare de caz și revizuirea literaturii

2016 ◽  
Vol 24 (3) ◽  
pp. 263-277
Author(s):  
Mihaela Cîrstea ◽  
Adriana Coliță ◽  
Bogdan Ionescu ◽  
Didona Vasilache ◽  
Camelia Dobrea ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Bone Marrow Aspirate ◽  
Chronic Myelomonocytic Leukemia ◽  
Hematopoietic Stem ◽  
Myelomonocytic Leukemia ◽  
Acute Myeloid

Abstract Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder that is characterized by the presence of an absolute monocytosis (1 × 10^ 9/l) in the peripheral blood, the overlap of myelodisplastic aspects and myeloproliferative aspects in the bone marrow and tendency to transform into acute myeloid leukemia. CMML is considered to be the most aggressive chronic myeloid leukemia. We present the case of a 48 years old woman who was hospitalized in March 2013 in the Center of Hematology and Bone Marrow Transplantation for anemia related symptoms. Initial investigations showed anemia, relative monocytosis (10% monocytes of the WBC differential) with an increasing absolute number of monocytes (> 1,000/μl) in the following months. Initial exploration of the bone marrow (aspirate and bone marrow biopsy and immunohistochemistry IHC tests) revealed elements of trilinear dysplasia and an increased percentage of myeloblasts (11-14%). In the next four months myeloblasts percentage remained below 20% (8-14%) and it has been observed a gradually increasing of monocytoid elements (> 20%). Immunophenotyping in the bone marrow aspirate identified a monocytic proliferation with high percentage (8%) of immature cells. The karyotype reported the presence of clones with t (1;3). Initially diagnosed as RAEB-2 (WHO) the case was recomitted in CMML-type 2 with a progression to acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been performed after getting the best possible therapeutic response with AML chemotherapy type (complete remission). Allo-HSCT was performed using myeloablative conditioning, 12 months after diagnosis. The patient is now in complete remission, 24 months after allo-HSCT.

Results of Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia of the FAB M0 Subtype in First Complete Remission: A Survey of the Acute Leukemia Working Party of the European Bone Marrow Transplant Group (EBMT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5131-5131
Author(s):  
Andree-Laure Herr ◽  
Myriam Labopin ◽  
Rosy Reiffers ◽  
Donald Bunjes ◽  
Didier Blaise ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients with acute myeloid leukemia (AML). AML of the FAB M0 subtype is rare, often associated with a complex karyotype and a poor prognosis. Results of HSCT for this AML subtype have never been reported separately from other subtypes. We did a survey of the results of 274 HSCT in adults with M0 AML in first complete remission (CR1), performed in EBMT centres since January 1990 until 2002. One hundred fifty patients were transplanted with an HLA identical donor (HLA-id), 30 with an HLA-matched unrelated donor (MUD) and 94 received an autologous transplant (auto). The median age was 45 years (16–71), the median interval from diagnosis to HSCT was 4 months for HLA-id, 6 months for MUD and 5 months for auto HSCT. The median follow-up time (range) was 20 months (1–109), 12 (2–53) and 10 months (1–96) for HLA-id, MUD and auto-HSCT respectively. The source of stem cells was peripheral blood stem cells for 67% of cases, and bone marrow for the remaining. The majority of grafts were non-T-cell depleted. Acute GVHD (grade I–IV) occurred in 56% of HLA-id and in 64% of MUD cases. The table shows the outcomes at two years according to the type of transplant. In conclusion, outcomes after HLA identical HSCT and MUD in adult patients with AML FAB subtype M0 in CR1 are encouraging. In comparison to allogeneic transplant cases, LFS is decreased in patients receiving an autologous transplant due to a high relapse incidence, reflecting the probable role of a graft-versus-leukemia effect in this FAB subtype. Results of HSCT in AML M0 CR1 patients Outcomes HLA-id n=150 MUD n= 30 Auto n=94 LFS: leukemia free survival; OS: overall survival; RI: relapse incidence; TRM: treatment-related mortality 2y LFS 50% 45% 33% 2y OS 58% 50% 49% 2y RI 25% 40% 57% 2y TRM 24% 14% 9%

A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia

Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 1166-1173 ◽  
Author(s):  
Gerald G. Wulf ◽  
Rui-Yu Wang ◽  
Ingrid Kuehnle ◽  
Douglas Weidner ◽  
Frank Marini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Side Population ◽  
Fluorescence Emission ◽  
Drug Efflux ◽  
Hematopoietic Stem ◽  
Immunodeficient Mice ◽  
Acute Myeloid

The hematopoietic stem cell underlying acute myeloid leukemia (AML) is controversial. Flow cytometry and the DNA-binding dye Hoechst 33342 were previously used to identify a distinct subset of murine hematopoietic stem cells, termed the side population (SP), which rapidly expels Hoechst dye and can reconstitute the bone marrow of lethally irradiated mice. Here, the prevalence and pathogenic role of SP cells in human AML were investigated. Such cells were found in the bone marrow of more than 80% of 61 patients and had a predominant CD34low/− immunophenotype. Importantly, they carried cytogenetic markers of AML in all 11 cases of active disease examined and in 2 out of 5 cases in complete hematological remission. Comparison of daunorubicin and mitoxantrone fluorescence emission profiles revealed significantly higher drug efflux from leukemic SP cells than from non-SP cells. Three of 28 SP cell transplants generated overt AML-like disease in nonobese diabetic–severe combined immunodeficient mice. Low but persistent numbers of leukemic SP cells were detected by molecular and immunological assays in half of the remaining mice. Taken together, these findings indicate that SP cells are frequently involved in human AML and may be a target for leukemic transformation. They also suggest a mechanism by which SP cells could escape the effects of cytostatic drugs and might eventually contribute to leukemia relapse.

Successful Salvage Treatment With Clofarabine and Cytarabine In Relapsed/Refractory Acute Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5039-5039
Author(s):  
Alessandra Malato ◽  
Francesco Acquaviva ◽  
Alessandra Santoro ◽  
Rosaria Felice ◽  
Silvana Magrin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Stem Cell Transplant ◽  
Remission Rate ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract Objectives Relapsed/refractory AML patients  have a poor prognosis; allogeneic hematopoietic stem cell transplantation (HSCT) is the only chance in this setting to achieve long-term disease-free survival (1). It was previously established the activity of clofarabine plus cytarabine in AML relapse (clofarabine dosed once daily for 5 days with 40 mg/m2  followed 4 hours later by ara-C at 1 g/m2 per day)(2).However, modifications of this combination in AML therapy of relapsed/refractory patients warrant further evaluation. Therefore, our goal was to determine the efficacy and safety of clofarabine at lower dosage followed by  cytarabine (Ara-C) in adult patients with relapsed or refractory acute myeloid leukemia (AML) and to evaluate the capacity of this regimen as a bridge for HSCT. Methods Patients aged 18-65 years with refractory/relapsed AML were treated at the dose of clofarabine 30 mg/mq on days 1-5 and cytarabine 1000 mg/mq gg on days 1-5. We evaluated the complete remission rate (CRR), duration of remission (DOR) and overall survival (OS). Minimal residual disease (MRD) by molecular targeting was considered in all patients. Results Twenty-five (25) patients aged 29-64 years (median 47), who were fit for allogenetic HCT,  received one cycle of 30 minutes infusion of  clofarabine 30 mg/mq, followed 4 hours later by 3 hours infusion of  intermediate dose cytarabine 1000 mg/mq  days 1-5. Only in the first three patients this schedule was followed by gentuzumab. Nine (36%) patients had refractory disease (seven after one induction regimen, one after two previous regimes, one after a prior hematopoietic stem cell transplant (HSCT);  16 (64%) patients  were in their first (12 patients) or second relapse (4 patients); among the 12 patients in first relapse, 5 were from an allogeneic stem cell transplant.  Fourteen patients (56%)  achieved a complete remission (CR), seven (28%) was refractory and 4 (16%) died of treatment related mortality. Eleven (44%) patients  underwent (9 in CR) to allogeneic transplants or DLI infusion (3 patients refractory, and 8 patients relapsed), only one  patient underwent to autologous transplant. One patient, who was relapsed after prior HSCT, obtained a CR but he developed acute  graft vs host disease after therapy  and died in molecular CR*.  Among all patients underwent HSCT after Clofa/Ara-c salvage, six patients (50%) are still alive and in complete remission, six patients (50%) died because of  HSCT complications or AML relapse. The complete remission rate (CRR) was  (56,00 %), the median  Overall Survival  was 5 months for all patients (range 1-38 M), 11 Months for those underwent to tranplantation and 1,5 Months for non transplanted group. Treatment was complicated by neutropenic fever (n=17), grade III-IV mucositis (n=2) , skin rush  (n=4) grade II- III, hepatic transaminase elevations (n=2).  Two (n=5) patient died before their disease status could be evaluated. Conclusions These preliminary results suggest that combination treatment with clofarabine 30 mg/mq and ARA-C 1000 mg/mq is effective in this particularly poor prognosis category of patients, resulting in an ORR very favorably,  representing a potential “bridge” toward bone marrow transplant procedures (among the 14 patients who achieved a CR, twelve (85%) proceeded to HSCT, and six are still alive). The safety profile is acceptable in this relapsed/refractory population, and our results are very similar to previous regimes using higher clofarabine dosages.  More studies with this combination in adults are warranted. References 1 Estey E. Treatment of relapsed and refractory acute myeloid leukemia. Leukemia. 2000;14:476-479. 2. Faderl S et al, “Results of a pase 1-2 study of clofarabine in combination with cytarabine (ara-C)”Blood 2005 Disclosures: No relevant conflicts of interest to declare.

scholarly journals αβ-T-cell-depleted haploidentical hematopoietic stem cell transplantation in children with chemorefractory acute myeloid leukemia

2019 ◽  
Vol 18 (2) ◽  
pp. 11-21
Author(s):  
L. N. Shelikhova ◽  
M. A. Ilushina ◽  
K. V. Semiglazova ◽  
Zh. B. Shekhovtsova ◽  
D. A. Shasheleva ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Primary refractory and relapsed refractory acute myeloid leukemia remains an unresolved problem in pediatric oncology. Children with AML who fail to achieve complete remission on high-dose cytarabine and antracyclines have no chance for survival without allogeneic hematopoietic stem cell transplantation. We evaluated the outcome of αβ-T-cell-depleted haploidentical transplantation in a cohort of children with chemorefractory acute myeloid leukemia. Thirty-six patients with either primary refractory (n = 14) or relapsed refractory (n = 22) acute myeloid leukemia in active disease status received a transplantation from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent treatment with treosulfan and either melphalan or thiophosphamide. Serotherapy consisted of antithymocyte globuline in 14 pts and targeted immunomodulation with tocilizumab +/- abatacept in 22 pts. Grafts were PBSCs engineered by TCR-αβ/CD19 depletion. Posttransplant preemptive therapy included modified donor lymphocyte infusions with or without hypomethylating agents. Complete remission was achieved in 30 (83%) рts. The cumulative incidence of acute GVHD grade II–IV was 25%, and the cumulative incidence of chronic GVHD was 18%. Transplant-related mortality was 6%, and relapse incidence was 48%. Event-free survival was 46%, and overall survival was 41% at 2 years. Good early recovery of NK cells was associated with significantly improved survival and decreased relapse incidence. Our data suggest that αβ-T-cell-depleted haploidentical HSCT provides a reasonable chance of cure in a cohort of children with chemorefractory acute myeloid leukemia and creates a solid basis for further improvement. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology.

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