Report Of Acute Myeloid Leukemia Research Articles

First Case Report of Acute Myeloid Leukemia with MN1-ETV6 Rearrangement at Relapse

Jae Joon Lee, M.D., Ha-Eun Cho, M.D., Kyung Sun Park, M.D., Young Jin Kim, M.D., Sun Young Cho, M.D., Jae Joon Han, M.D., Woo-In Lee, M.D., Tae Sung Park, M.D.. Lab Med Online 2021;11:145-8. https://doi.org/10.47429/lmo.2021.11.2.145

EP026 - Case report of acute myeloid leukemia and dilated cardiomyopathy in a pediatric patient with D-2-hydroxyglutaric aciduria type I

eP026 - Case report of acute myeloid leukemia and dilated cardiomyopathy in a pediatric patient with D-2-hydroxyglutaric aciduria type I

First Description of Upfront Target Therapy Treating AML and Bcll Presented Simultaneously As First Line

INTRODUCTION: The occurrence of acute myeloid leukemia (AML) and chronic lymphoid leukemia (B-CLL) simultaneously is rarely described. We describe a case report of AML and B-CLL, diagnosed simultaneously, without any previous treatment for any of the hematological neoplasms [1]. The patient received low-dose cytarabine (ARA-C) and Venetoclax, which is medically indicated on label for both hematological neoplasms. CASE REPORT: A 75-year-old male, presented with edema and joint pain one month before hospital admission, showing pancytopenia on a complete blood count and presence of blasts in peripheral blood. The patient was then referred to the hematology service. The morphological analysis of the bone marrow aspirate showed 67.7% of myeloblasts, compatible with AML. Bone marrow immunophenotyping was performed, which identified 34.10% of myeloblasts, compatible with AML and 50.48% of monoclonal B lymphocytes (chronic B-cell lymphoproliferative disease). In flow cytometry there were two distinct populations of myeloblasts. Type 1 myeloblasts labeling CD7 +, CD13 +, CD34 ++, CD38 ++, CD45 ++, CD56 ++, CD117 ++, CD123 +, HLA-DR +++ and MPO + / ++. The second population marked CD13 + / ++, CD34 + / ++, CD38 ++, CD45 +, CD117 ++, CD123 +, HLA-DR ++ / +++ and MPO + (30%). Monoclonal lymphocytes showed CD11c + / ++ (70%), CD19 ++, CD20 + / ++ (84%), CD22 + (39%), CD23 + / ++, CD25 +, CD31 +/-, CD43 ++, CD45 ++ / +++, CD81 + (38%), CD200 + (85%) and Lambda +. The molecular study was negative for genetic abnormalities: FLT3, KIT and NPM, configuring the patient as an intermediate risk for AML. In the cytogenetic analysis there was no growth of metaphases. Patient received simultaneous diagnosis of AML and B-CLL. As he was ineligle to intensive chemotherapy (IC), we started original protocol Subcutaneous Cytarabin+venetoclax(VIALE C). The patient had grade 2-3 AE(neutropenia managed with GCSF) ending the fourth cycle in July 2020. The evolution of hematimetric parameters and diseases are described in graphics. DISCUSSION: This is the first described case in our knowledge treated upfront with bcl2-inh target therapy for two absolutely different hematological neoplasms: AML and BCLL. Nowadays we are experiencing a new therapeutic model in oncohematology, in which the targeted therapy is gaining ground in relation to IC with excellent results. In this way, the importance of comprehension of the pathophysiological mechanism of the neoplasms and the way we can stop the disease proliferation is progressively guiding the new protocols. Elderly patients are more likely to have early treatment-related death and exhibit therapeutic resistance, limiting alternatives. We decided to start first-line treatment with ARA-C and Venetoclax [2]. Venetoclax associated with ARA-C has a manageable safety profile, producing quick and durable remissions in elderly people with AML ineligible for IC, as well as in B CLL, being the best therapeutic alternative for the case, in our opinion. Venetoclax belongs to a group of drugs called Bcl-2 inhibitors, an anti-apoptotic protein, which works by blocking this protein in the body, causing apoptosis of both neoplastic cells. The high rate of remission and low early mortality, combined with fast and durable remission, make Venetoclax and ARA-C a new and attractive treatment for the elderly [2]. In our case, the intention of the product in the first line was not B-CLL, but it would certainly be a good option for this profile of elderly patients. CONCLUSION: We report the first description of simultaneous diagnosis of AML and B CLL treated with a Bcl-2 inhibitor, demonstrating that antitumor mechanisms can be extremely effective in completely different diseases. We have a long way to go in the search for full knowledge of oncohematological diseases and targeted therapies. However, this case report shows that we are on the right track.

Female reproductive potential after oncological treatment: a rare case report of acute myeloid leukemia in monozygotic twin sisters with literature review

BackgroundAcute myeloid leukemia (AML) in monozygotic twins is a rare event and, until now, only a few cases have been reported. Due to improved oncological treatment and cancer survival rates, quality of life considerations post-treatment have become an important aspect in the treatment regime. The ability to have their own biological children is considered one of the most important indicators of quality of life by cancer survivors. As fertility following oncological treatment is often impaired, fertility preservation methods should be offered to these patients prior to the treatment. Here, we present a very rare case in which we can in vivo observe the impact of oncological treatment on female fertility when applied before and after puberty.Case presentationThis is a very rare case of concordant AML in monozygotic twin sisters. Twin A became sick at the age of 21 months. She was treated with cytostatic medications and then underwent bone marrow transplantation (BMT), the donor being her twin sister B. After 27 years, she is disease free and has regular periods. After trying to conceive for 4 years, she was seen by an infertility specialist. She underwent hysteroscopic uterine septum removal and laparoscopic enucleation of bilateral paraovarian cysts. Following those procedures, she immediately conceived naturally. Twin B became sick at 15 years of age. She was treated with chemotherapy and cranial radiation and relapsed after 10 years. She then received chemotherapy and had a BMT. Until relapse, she had normal menstrual cycles. After the second treatment she became amenorrhoeic and is now part of an oocyte donation program.ConclusionsThis is a case of AML in monozygotic twins who, after treatment, have completely different reproductive potential. They both received oncological treatment, and one of them conceived conceived naturally while the other suffered premature ovarian failure and is not able to have a biological child. Based on the outcome of this case, it appears that the pre-pubertal state truly serves as protection against ovarian failure.

Case Report of acute myeloid leukemia with “WT1, ATRX, CEBPA, CSMD1, IKZF1, and LRP1B mutation and translocation between chromosome 1 and 19” developing from Philadelphia-negative chronic myeloid leukemia after TKI therapy

Rationale:The success of tyrosine kinase inhibitor (TKI) therapy has greatly prolonged the survival time of patients with chronic myeloid leukemia (CML), harboring the characteristic Philadelphia (Ph) chromosome. However, a fraction of patients, achieving complete cytogenetic response after TKI therapy, develop a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with additional clonal chromosomal abnormalities in Philadelphia-negative cells (CCA/Ph–).Patient concerns:A 56-year-old woman with AML, developing from Philadelphia-negative CML after TKI therapy. She showed 6 kinds of somatic variants—CEBPA, ATRX, WT1, CSMD1, IKZF1, and LRP1B mutation after diagnosed as AML.Diagnosis:The patient was diagnosed with chronic phase CML that developed to AML after achieving durable complete cytogenetic response (CCR) and major molecular response (MMR).Interventions:The patient was treated with TKI therapy at the period of CML. When diagnosed with AML, she received induction chemotherapy regimens, consolidation therapy, and allogeneic hematopoietic stem cell transplantation subsequently.Outcomes:The patient has been CCR and MMR for nearly 4 years, and has achieved complete remission after intervention related to AML. She is now preparing for allogeneic hematopoietic stem cell transplantation.Lessons:These rare occurrences highlight the importance of exploring the relevant pathogenesis of AML developing from CML after TKI therapy. In addition to monitoring molecular changes in the course of CML, cytogenetic analysis, or next-generation sequencing of CML patients should be performed.

A case report of acute myeloid leukemia metastasized to the spinal canal

A case report of acute myeloid leukemia metastasized to the spinal canal

Therapy-related acute myeloid leukemia in a patient with chronic lymphocytic leukemia treated with rituximab–bendamustine

Dear Editor, Therapy-related neoplasms account for 10–20 % of all cases of acute myeloid leukemias (AMLs). Two subsets of therapy-related acute myeloid leukemias are generally recognized. The most common occurs 5–10 years after exposure to alkylating agents and/or ionizing radiation. The second category has a latency period of about 1–5 years and follows treatment with agents that interact with DNA topoisomerase II. Herein, we present the clinical case of a patient with chronic lymphocytic leukemia (CLL) who developed acute myeloid leukemia after treatment with bendamustine, an alternative agent with both alkylating and purine-like qualities. To our knowledge, this is the first report of acute myeloid leukemia induced by bendamustine. A 62-year-old patient was diagnosed with CLL, clinical stage I-A Rai–Binet in December 2009; however, absolute lymphocytosis had previously been detected in October 2006. Bone marrow infiltration reached 59 % of atypical lymphocytes with a Matutes score of 3/5 in immunophenotype. Peripheral blood and bone marrow had atypical lymphocytes, but no dysplastic morphologic alteration was observed. Cytogenetic aberrations were detected in 50 % of cells with 46,XY, der (3)(p?),-8. FISH analysis detected del (13)(q14) in 73 % of the analyzed nuclei without del (11q), del (17p), or trisomy 12. CLL lymphocytes used the gene IGHV330-3 with only 93.4 % of homology. The patient remains in observation with a diagnosis of CLL with genomic aberrations (13q deletion) and mutated IGHV genes without symptoms and good prognosis (Table 1). In October 2011, he received treatment with four cycles of rituximab (375mg/m, day 1) and bendamustine (90 mg/m, days 1–2) for severity of CLL characterized by progressive lymphadenopathy, massive splenomegaly (23 cm), and a lymphocyte count of 71,000/μl. The last cycle was administered at a lower dose of bendamustine (70mg/m, days 1–2). The patient reached a complete response evaluated by CT (ESM Fig. 1) and negative minimal residual disease in bone marrow measured by flow cytometry in February 2012. Interestingly, severe T cell lymphopenia was detected even at 8 months after treatment (Table 2). In July 2012, mild thrombocytopenia and monocytosis (platelets 92,000/μl, monocytes of 4,800/μl) without symptoms were detected. A peripheral blood smear showedmonocytosis but without blasts. Two months later, the patient presented worsening of the pancytopenia with Hb 10.1 g/dl, 98,000 platelets/μl and leukocytes 12,000/μl, neutrophils 700/μl, lymphocytes 6,200/μl, and monocytes 5,700/μl as well as mild asthenia. At this moment, the patient presented 20 % of blasts with only mild signs of dysplasia in peripheral blood smear (Fig. 1). A bone marrow aspiration was performed demonstrating infiltration of 89 % of monoblasts and promonocytes with abundant cytoplasm and azurophilic granules. Mild signs of dysplasia were seen occasionally in BM (Figs. 2 and 3). Multiparametric flow Electronic supplementary material The online version of this article (doi:10.1007/s00277-013-1844-8) contains supplementary material, which is available to authorized users. R. Garcia-Munoz (*) :D. K. Garcia :V. Roldan-Galiacho : A. Campeny-Najara : P. Rabasa Hematology Service, Hospital San Pedro, Calle Piqueras 98, 26006 Logrono, La Rioja, Spain e-mail: rgmunoz@riojasalud.es

A Case Report of Acute Myeloid Leukemia and Neurofibromatosis 1

We report a case of a 65-year old patient affected by neurofibromatosis 1, documented by the presence of germ-line mutation on the NF1 gene, who developed various hyperproliferative malignant and benign diseases. He was brought to our attention for the diagnosis of acute myeloid leukemia revealed by major fatigue and dyspnea. The disease characteristics at diagnosis were hyperleukocytosis and complex karyotype with the inversion of the chromosome 16, classifying as a high-risk leukemia. The association between leukemia and neurofibromatosis 1 is controversial and needs to be further investigated. Nevertheless, such patients present a wide number of comorbidities that make therapeutic strategies most difficult.

Acute Myeloid Leukemia with t(2;6)(q12;q12) Reveals Dysmegakaryopoietic Finding and Poor Prognosis

We present a case of acute myeloid leukemia (AML) with a balanced translocation between chromosomes 2q12 and 6q12, t(2;6)(q12;q12). This abnormality was defined by conventional cytogenetics and multicolor banding techniques using specific probes for chromosome 2. Blasts accounted for 2% of white blood cells in peripheral blood and approximately 30% of all nucleated cells in marrow aspirates. They were medium-to-large cells with fine nuclear chromatin, indistinct nucleoli and basophilic cytoplasm. Immunophenotyping indicated the blasts were of myeloid lineage with aberrant CD7 expression. Therefore, the patient was diagnosed as ‘Acute myeloid leukemia, NOS, AML with maturation’ according to the WHO classifications. In literature review, this case should be considered as the first report of AML with t(2;6)(q12;q12). Interestingly, a bone marrow smear showed dysmegakaryopoietic findings, such as multinucleated or mononucleated megakaryocytes and micromegakaryocytes. After diagnosis, the induction chemotherapy was given with idarubicin and cytosine arabinoside according to the protocol of intermediate-prognostic AML. After chemotherapy, the patient had been in remission for 13 months but relapsed with 54% blasts in marrow aspirates. The cytogenetic analysis revealed t(2;6)(q12;q12), which is same with karyotype shown at diagnosis. In this case report, the pathologic and clinical findings of AML with t(2;6)(q12;q12) were described, which are severe dysmegakaryopoiesis and poor prognosis. This report may be helpful for clinician to have a similar case treated

Case Report Case report of isochromosome 17q in acute myeloid leukemia with myelodysplasia-related changes after treatment with a hypomethylating agent

Isochromosome 17q is a relatively common karyotypic abnormality in medulloblastoma, gastric, bladder, and breast cancers. In myeloid disorders, it is observed during disease progression and evolution to acute myeloid leukemia in Philadelphia-positive chronic myeloid leukemia. It has been reported in rare cases of myelodysplastic syndrome, with an incidence of 0.4-1.57%. Two new agents have been approved for treatment of myelodysplastic syndrome/chronic myelomonocytic leukemia. These are the hypomethylating agents, 5-azacytidine and decitabine, recommended by consensus guidelines for high-risk myelodysplastic syndrome patients not eligible for hematopoietic stem cell transplantation. We present a case of chronic myelomonocytic leukemia with normal cytogenetics at diagnosis treated with decitabine (with good response); however, the patient evolved to acute myeloid leukemia with i(17q) shortly after suspending treatment. To the best of our knowledge, this is the first report of acute myeloid leukemia with myelodysplasia-related changes with i(17q) after the use of a hypomethylating agent.

Acute Myeloid Leukemia in Mice Associated with Retrovirally-Mediated Overexpression of HOXB4

Numerous studies have established that retrovirally-mediated overexpression of the homeobox gene HOXB4 in murine bone marrow cells (BMCs) enhances expansion of hematopoietic stem cells (HSCs) in vivo and in vitro without causing hematopoietic abnormalities or impairing the ability of HSCs to give rise to differentiated progeny. More recently, however, retrovirally-mediated overexpression of HOXB4 in BMCs of large animals, such as dogs and macaques, has been implicated in leukemogenesis, but there are no prior reports of such a phenomenon occurring in mice transplanted with HOXB4-transduced BMCs. We report here two independent occurrences of acute myeloid leukemia (AML) in mice that received transplants of BMCs transduced with a HOXB4-overexpressing retrovirus. 5-FU treated BMCs were transduced with a MSCV-HOXB4-IRES-GFP retrovirus and transplanted into lethally irradiated mice. Two of the 54 mice (#1869 & #2050), transplanted with HOXB4-transduced BMCs, developed AML at 4 and 9.5 months, respectively, following transplantation. None of the 90 control mice, transplanted with BMCs transduced with the parent MSCV-IRES-GFP retrovirus, developed leukemia. Leukemia 1869 (L1) manifested marked leukocytosis, thrombocytopenia and mild anemia. Results of morphological and immunophenotyping analyses of bone marrow were consistent with AML. Leukemia 2050 (L2) also showed marked leukocytosis and significant anemia, but a near normal platelet count. Morphological analysis revealed a myelomonocytic phenotype, while immunophenotying showed the presence of multi-lineage cell surface markers, including myeloid (CD11b, Gr-1), erythroid (Ter119), and B lymphoid (B220) markers. A small percentage of cells that expressed the stem cell markers c-kit and Sca1 were identified in both leukemias. Both leukemias could be passaged by serial transplantation of leukemic bone marrow or spleen cells into wild type recipient mice. Analysis of retroviral integration sites identified ten separate integration sites in L1 and two in L2. This correlated with 6 fold higher levels of HOXB4 mRNA in L1 BMCs compared to L2 BMCs, as assessed by northern blot analysis that showed undetectable levels of HOXB4 mRNA in RNA of control BMCs. Some of the integration sites occurred in introns of genes known to be involved in leukemogenesis and resulted in aberrant expression of these genes. In L1, one of the retroviral integration sites occured in intron 1 of the N-ras gene and was associated with markedly increased levels of its mRNA in RNA of leukemic BMCs (15–20 fold higher levels compared to that in control BMCs). Another integration site in L1 was in intron 2 of the Lmo2 gene and was associated with a mild (~2 fold) increase in its mRNA level in leukemic cells. In L2, one of the retroviral integration sites was in intron 1 of the Prdm16 gene and was associated with markedly increased levels of its mRNA in leukemic cells. The second retroviral integration site in L2 was located ~50 kb upstream of the Notch1 gene and there was ~2 fold increase in its mRNA in BMCs of leukemic mice. We speculate that overexpression of HOXB4 acts in a cooperative or combinatorial fashion with overexpression of proto-oncogenes at the retroviral integration sites to induce AML in these mice. To test this hypothesis, we are testing various culture conditions to allow viable growth of the leukemic cells ex vivo and assess the effects of knockdown of HOXB4 mRNA accumulation on growth and differentiation of the cells in vitro, as well as on their ability to transmit leukemia in vivo. We are also characterizing the nature of the cells in the total leukemic cell population that are associated with in vivo leukemia-initiating activity. This is the first report of AML in mice associated with retrovirally-mediated overexpression of HOXB4.

Isodicentric Chromosome 21: A Novel Aberration in Acute Myeloid Leukemia

We present here a 78-year-old female patient with acute myeloid leukemia (AML), French-American-British classification M2, exhibiting isodicentric chromosome 21, idic(21)(q22), at the time of diagnosis. The patient had three idic(21)(q22), besides the del(5)(q13q32), add(21)(q22), dic(21;22) (q22; q13), and +22. Fluorescence in situ hybridization studies with whole-chromosome painting and centromere-specific probes for chromosome 21 verified the diagnosis of idic(21)(q22). There were no distinct clinicohematological characteristics of AML with isodicentric 21. The patient was treated with remission-induction therapy followed by consolidation therapy. Two years later, the patient showed the disappearance of isodicentric 21 but retained del(5)(q13q32) and gained other chromosomal abnormalities, +add(17)(p11) and −16. To our knowledge, this is the first report of AML with acquired idic(21)(q22).

Is trisomy 22 in acute myeloid leukemia a primary abnormality or only a secondary change associated with inversion 16?

In an attempt to confirm the existence of acute myeloid leukemia (AML) with trisomy 22, we studied three patients in whom trisomy 22 imposed as the sole karyotype abnormality. After revision of the karyotypes, however, we were able to identify an inv(16) as the important primary abnormality in all of them. Based on this experience, we investigated whether at least some of the 17 AML cases with trisomy 22 reported so far might possibly have been misinterpreted. Interestingly, ten out of 16 evaluable cases were classified as M4, some of them with bone marrow eosinophilia. As in cases with inv(16), only few metaphases contained trisomy 22. Furthermore, in at least two out of the only four published karyotypes of cases with trisomy 22, an inv(16) is evident and in the other two cases it cannot be ruled out. We therefore believe that at least some of the trisomy 22 cases mentioned in the literature are in fact only secondary changes occurring in AML with an inv(16) and suggest that future reports of AML with trisomy 22 as a specific primary abnormality can only be accepted as such if inv(16) has been excluded with appropriate methods.