scholarly journals Lineage switch from acute myeloid leukemia to T cell/myeloid mixed phenotype acute leukemia: First report of an adult case

2018 ◽  
Vol 93 (12) ◽  
pp. E395-E397 ◽  
Author(s):  
Brian P. Hanley ◽  
Eva Yebra-Fernandez ◽  
Renuka Palanicawandar ◽  
Eduardo Olavarria ◽  
Kikkeri N. Naresh
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Adult Case ◽  
First Report ◽  
Lineage Switch ◽  
Mixed Phenotype Acute Leukemia ◽  
Mixed Phenotype ◽  
Acute Myeloid

scholarly journals Uncommon CD markers in acute myeloid leukemia

2018 ◽  
Vol 11 (4) ◽  
pp. 267-269
Author(s):  
Azad Abul Kalam ◽  
Md. Rafiquzzaman Khan ◽  
A. B. M. Hassan Habib ◽  
Masuda Begum
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Color Flow ◽  
Mixed Phenotype Acute Leukemia ◽  
International Data ◽  
Mixed Phenotype ◽  
Cd Markers ◽  
Acute Myeloid

This study was done to assess the unusual CD expression in 100 cases of acute myeloid leukemia from October 2016 to April 2018. The age limit was from 3 to 50 years. Four color flow cytometry was used to diagnose the fresh aspirated bone marrow or peripheral blood sample of acute leukemia. The unusual lymphoid CD expression on myeloblasts was analyzed. Among the cases, 44% were acute myeloid leukemia, 52% of patients were of acute lymphoblastic leukemia and mixed phenotype acute leukemia was 4%. Aberrant CD expression was observed in 58% acute myeloid leukemia patients. Both aberrant CD5 and CD7 lymphoid markers expressed in acute myeloid leukemia patients were 4.2%. Aberrant CD7, CD5, cCD79a and cCD3 were in 45.8%, 33.3%, 8.3%, 8.3% of acute myeloid leukemia patients respectively. In acute myeloid leukemia, the frequency of aberrant CD expression was compared with recent international data.

scholarly journals Clinical Characteristics and Outcomes of 82 Patients with Mixed-Phenotype Acute Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1124-1124
Author(s):  
Yan chun Yang ◽  
Ya Gao ◽  
Ying Xu ◽  
Yintian Zhang ◽  
Dongmao Zhu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Guangdong Province ◽  
Hybrid Therapy ◽  
Mixed Phenotype Acute Leukemia ◽  
Mixed Phenotype ◽  
Acute Myeloid

Abstract Objectives: Mixed-phenotype acute leukemia(MPAL) is a rare disease and comprises 2% to 5% of all acute leukemia. Outcomes for MPAL are worse than both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).The complex phenotype exhibited by this type of leukemia resulted in a myriad of treatment approaches.In our study, we retrospective analysis 82 patients in clinical trail, treatment strategy and prognosis. Method: eighty-two patients diagnosed with MPAL at Nan fang hospital from 2006 to 2017 using either EGIL or 2008 WHO criteria were analyzed. Comparison the treatment effect and outcomes between different therapy types. Result: eighty-two patients, including 60 males and 22 females with a median age of 29 years (range, 2 months-72 years), were studied. 61 patients (77%) were older than 18years, 73patients met the criteria for MPAL via EGIL, 68via WHO2008, and 59of these were reported to satisfy both definitions. fifty one of these cases (62.2%) had a B/myeloid phenotype, Twenty four of these cases (29.3%) had a T/myeloid phenotype. The other cases (8.5%) showed immunophenotypic evidence of a B, T, and myeloid lineage in one blast population. Among the 82 cases, 57 cases with successful cytogenetic studies, 20(35.1%) had normal karyotypes and 37patients(64.9%) had abnormal karyotypes. Twelve patients (21.05%) translocation between chromosomes 9 and 22, five (8.8%) patients had 11q23/MLL translocations. Twelve patients (21.05%) had a complex karyotype and eight patients (14%) had other karyotype. The rarity of this disease and the fact that patients with MPAL are excluded from most AML and ALL clinical trials further complicates guidance about therapy. Of the 82 cases, 75 patients underwent the complete first course of treatment and complete remission rate was 49.8%. treatment approaches utilizing therapy for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and so-called "hybrid" therapy mixing elements of both are 51.9%, 16.7% and 66.7% respectively (P=0.003).OS and EFS with hybrid induction therapy and ALL like induction were not significantly different than those with AML induction by either definition (P>0.05). A total of 60 patients received consolidation treatment, 21 patients received the chemotherapy while 39 patients received stem cell transplant (HSC). The total Median EFS was 21months, in Chemotherapy group and HSC group, the Median EFS was 6 months and 40 months respectively, The 3-year EFS was 26.1% and 55.6% respectively (P=0.038). The total Median OS was 21 months, Median OS showed a significant survival benefit for starting with chemotherapy as compared to HSC( 12 months and 43 months respectively (P=0.001)), The 3-year OS was 19.1% and 57.7% respectively. Conclusion: In this study, ALL like induction therapy or "hybrid" therapy was associated with a more than three-fold greater CR rate than AML therapy. SCT therapy showed a trend for an association with higher OS and EFS for MPAL . Key words: MPAL, Immunophenotype,Treatment strategy Funding Key Sci-Tech Research Projects of Guangdong Province (2014A02021102). Disclosures Fan: National Natural Science Foundation of China (No. 81600141, No. 81770190) and Natural Science Foundation of Guangdong Province (No. 2016A030310390): Research Funding.

Improved Outcome With T-Cell–Depleted Bone Marrow Transplantation for Acute Leukemia

1999 ◽  
Vol 17 (5) ◽  
pp. 1545-1545 ◽  
Author(s):  
Franco Aversa ◽  
Adelmo Terenzi ◽  
Alessandra Carotti ◽  
Rita Felicini ◽  
Roberta Jacucci ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Antithymocyte Globulin ◽  
Lymphoblastic Leukemia ◽  
Acute Myeloid

PURPOSE: To eliminate the risk of rejection and lower the risk of relapse after T-cell–depleted bone marrow transplants in acute leukemia patients, we enhanced pretransplant immunosuppression and myeloablation. PATIENTS AND METHODS: Antithymocyte globulin and thiotepa were added to standard total-body irradiation/cyclophosphamide conditioning. Donor bone marrows were depleted ex vivo of T lymphocytes by soybean agglutination and E-rosetting. This approach was tested in 54 consecutive patients with acute leukemia who received transplants from HLA-identical sibling donors or, in two cases, from family donors mismatched at D-DR. No posttransplant immunosuppressive treatment was given as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Neither graft rejection nor GVHD occurred. Transplant-related deaths occurred in six (16.6%) of 36 patients in remission and in seven (38.8%) of 18 patients in relapse at the time of transplantation. The probability of relapse was .12 (95% confidence interval [CI], 0 to .19) for patients with acute myeloid leukemia and .28 (95% CI, .05 to .51) for patients with acute lymphoblastic leukemia who received transplants at the first or second remission. At a median follow-up of 6.9 years (minimum follow-up, 4.9 years), event-free survival for patients who received transplants while in remission was .74 (95% CI, .54 to .93) for acute myeloid leukemia patients and .59 (95% CI, .35 to .82) for acute lymphoblastic leukemia patients. All surviving patients have 100% performance status. CONCLUSION: Adding antithymocyte globulin and thiotepa to the conditioning regimen prevents rejection of extensively T-cell–depleted bone marrow. Even in the complete absence of GVHD, the leukemia relapse rate is not higher than in unmanipulated transplants.

scholarly journals Biphenotypic Acute Leukemia versus Myeloid Antigen-Positive ALL: Clinical Relevance of WHO Criteria for Mixed Phenotype Acute Leukemia

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
William A. Hammond ◽  
Pooja Advani ◽  
Rhett P. Ketterling ◽  
Daniel Van Dyke ◽  
James M. Foran ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Diagnostic Criteria ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Transplant ◽  
Who Criteria ◽  
Mixed Phenotype Acute Leukemia ◽  
Mixed Phenotype ◽  
Biphenotypic Acute Leukemia ◽  
Acute Myeloid

Updated WHO criteria define mixed phenotype acute leukemia (MPAL) with more stringent diagnostic criteria than the formerly described entity biphenotypic acute leukemia (BAL). The changes in diagnostic criteria influence management by assigning weight to aberrantly expressed markers and minimizing expression of myeloid markers other than myeloperoxidase (MPO), potentially foregoing consolidative allogeneic transplant for an otherwise “favorable” lymphoid phenotypic leukemia. We present a case of MPO-negative, myeloid antigen-positive acute lymphoblastic leukemia who progressed with refractory phenotypic acute myeloid leukemia while receiving lymphoid-directed therapy and discuss concerns raised by the adoption of the new, more stringent diagnostic criteria for BAL.

scholarly journals Measurable residual disease status and outcome of transplant in acute myeloid leukemia in second complete remission: a study by the acute leukemia working party of the EBMT

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Maria H. Gilleece ◽  
Avichai Shimoni ◽  
Myriam Labopin ◽  
Stephen Robinson ◽  
Dietrich Beelen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Working Party ◽  
T Cell Depletion ◽  
Measurable Residual Disease ◽  
Acute Myeloid

AbstractMeasurable residual disease (MRD) prior to hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML) in first complete morphological remission (CR1) is an independent predictor of outcome, but few studies address CR2. This analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation registry assessed HCT outcomes by declared MRD status in a cohort of 1042 adult patients with AML CR2 at HCT. Patients were transplanted 2006–2016 from human leukocyte antigen (HLA) matched siblings (n = 719) or HLA 10/10 matched unrelated donors (n = 293). Conditioning was myeloablative (n = 610) or reduced-intensity (n = 432) and 566 patients (54%) had in-vivo T cell depletion. At HCT, 749 patients (72%) were MRD negative (MRD NEG) and 293 (28%) were MRD positive (MRD POS). Time from diagnosis to HCT was longer in MRD NEG than MRD POS patients (18 vs. 16 months (P < 0.001). Two-year relapse rates were 24% (95% CI, 21–28) and 40% (95% CI, 34–46) in MRD NEG and MRD POS groups (P < 0.001), respectively. Leukemia-free survival (LFS) was 57% (53–61) and 46% (40–52%), respectively (P = 0.001), but there was no difference in terms of overall survival. Prognostic factors for relapse and LFS were MRD NEG status, good risk cytogenetics, and longer time from diagnosis to HCT. In-vivo T cell depletion predicted relapse.

The Combined Expression of AML1-ETO and Oncogenic RAS Is Insufficient To Induce Acute Myeloid Leukemia (AML).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2557-2557
Author(s):  
Christian Flotho ◽  
Weili Sun ◽  
Sheila Shurtleff ◽  
Shouli Yang ◽  
James R. Downing
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Acute Leukemia ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Regulatory Sequences ◽  
Oncogenic Ras ◽  
Acute Myeloid

Abstract To define the leukemic potential of AML1-ETO, we recently generated a mouse strain with a conditional loxP-stop-loxP (LSL)-AML1-ETO knock-in allele that can be activated in hematopoietic cells by Cre-mediated recombination. Expression of AML1-ETO under these conditions readily induced the immortalization of multipotential hematopoietic progenitors, but failed to induce overt leukemia. Induction of secondary mutations with the alkylating agent ENU, however, resulted in the development of an acute leukemia similar to human t(8;21)-AML. Immortal AML1-ETO expressing non-leukemic cells grew as growth factor-dependent cell lines, where as the murine AML1-ETO expressing leukemias grew as growth factor-independent cell lines. This suggested that alterations in growth factor signaling pathways may cooperate with AML1-ETO to induce full transformation. Consistent with this interpretation, we have recently demonstrated that ~50% of core-binding factor leukemias have activating mutations in NRAS or KRAS. To directly assess the cooperativity of AML1-ETO and oncogenic Ras, we crossed the AML1-ETO / Mx1-Cre mice with a strain containing a LSL-KrasG12D knock-in allele. Expression of these two oncoproteins was induced simultaneously by Cre-mediated deletion of the upstream transcriptional stop cassettes. Importantly, expression levels for both genes depended on their respective endogenous regulatory sequences. As reported by others, activation of the LSL-KrasG12D allele alone resulted in the development of a lethal myeloproliferative disease (MPD), with all mice dying within 120 days (n=17). Triple transgenic mice (LSL-AML1-ETO / Mx1-Cre / LSL-KrasG12D, n=14) also died within 120 days of activation of both conditional alleles. Like the Mx1-Cre / KrasG12D only mice, the triple transgenic mice developed an MPD characterized by leukocytosis, anemia, splenomegaly and hepatic periportal leukocyte infiltrates. Surprisingly, no significant differences were noted in the frequency, latency, or phenotype of the MPD that developed in mice expressing either KrasG12D alone or both AML1-ETO and KrasG12D. Moreover, no AML was observed in the AML1-ETO and KrasG12D expressing mice. We further examined the cooperativity between these two oncoproteins by expressing a human NRASG12D cDNA through an MSCV-based retroviral vector that coexpressed a Cre-GFP fusion protein (MSCV-NRASG12D-IRES-Cre-GFP). Transduced bone marrow cells were transplanted into lethally irradiated mice and the recipients monitored for the development of disease. Expression of mutant NRASG12D by itself efficiently induced the development of a rapidly fatal MPD and a T-cell lymphoma/leukemia in the majority of transplanted mice. However, we again were unable to obtain any evidence for collaboration between NRASG12D and AML1-ETO. The clinical presentation as well as the morphology and immunophenotype of the myeloproliferative process were essentially identical between NRASG12D and AML1-ETO / NRASG12D induced disease. The only difference observed was a reduced incidence of T-cell disease in the AML1-ETO expressing mice, explicable by the previously published finding that AML1-ETO is toxic to developing T-cells. The results demonstrate that despite the frequent occurrence of RAS mutations in AML1-ETO expressing human AML, the coexpression of these two oncoproteins in mice using the experimental approaches described fails to induce an acute myeloid leukemia. These data suggest that these two oncogenic alterations require additional genetic lesions to induce acute leukemia.

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