Hypocellular Acute Myeloid Leukemia Research Articles

Immunoexpression of CD34, CD117, and p53 in Hypocellular Bone Marrow Disorders.

Objectives Hypocellular bone marrow (BM) disorders comprise heterogeneous entities associated with peripheral cytopenias and decreased production of hematopoietic cells in BM. This study was undertaken to analyze immunohistochemical expression of CD34, CD117, and p53 in morphologically diagnosed patients of hypocellular BM (aplastic anemia [AA], hypocellular myelodysplastic syndrome [h-MDS], and hypocellular acute myeloid leukemia [h-AML]). Materials and Methods BM specimens were obtained from patients presenting with pancytopenia/bicytopenia. On 30 patients diagnosed as hypocellular BM, immunohistochemistry (IHC) for CD34, CD117, and p53 was performed. Results BM cellularity was < 30% in all (100%) patients. Blast count was increased in h-MDS and h-AML. Features of dysplasia were noted in six (20%) patients. Out of these, three patients were diagnosed as h-MDS having bilineage/trilineage dysplasia, and the other three patients were of AA (11.5% patients) displaying only dyserythropoiesis. On IHC, percentage of BM CD34+ cells was increased in h-MDS+ h-AML (3.87 ± 0.86) as compared with AA (0.19 ± 0.15) and controls (0.81 ± 0.21), p = 0.01. Percentage of BM p53+ cells was also increased in h-MDS+ h-AML (2.9 ± 2.07) as compared with AA and controls, which did not show any p53+ cells, p = 0.0. No statistically significant difference was observed in the expression of CD117 in h-MDS+ h-AML (4.95 ± 3.40) compared with AA (4.49 ± 1.07), p = 0.99. Conclusion The study demonstrates the usefulness of CD34 and p53 immunoexpression as an important ancillary method in distinguishing various hypocellular BM disorders, especially h-MDS and AA. However, the role of CD117 remains unclear and needs to be evaluated further by larger studies.

Clinical features and outcomes of hypocellular acute myeloid leukemia in adults: A Korean AML registry data.

The hypocellular variant of acute myeloid leukemia (AML) is defined as bone marrow cellularity of <20% in a biopsy specimen at presentation. We performed a retrospective analysis of the clinical features and survival outcomes of hypocellular AML in a Korean population. We reviewed the medical records of all patients diagnosed with AML at nine hospitals participating in the Korean AML registry from 2006 to 2012. Overall survival (OS) and event-free survival (EFS) rates were calculated from the time of diagnosis until death or an event, respectively. In total, 2110 patients were enrolled and 102 (4.8%) were identified as having hypocellular AML. Patients with hypocellular AML were older than those with non-hypocellular AML (median age: 59 vs 49 years; P < .001) and presented with leukopenia more frequently (mean white blood cell count: 5810/μL vs 40549/μL; P < .001). There was no difference between patients with and without hypocellular AML in terms of the presence of antecedent hematologic disorders (5.9% vs 5.3%; P = .809). FLT3-ITD and NPM1 mutations were less common in hypocellular than non-hypocellular AML (FLT3-ITD mutations: 1.2% vs 14.3%, P < .001; NPM1 mutations: 0% vs 9.5%, P = .019). No differences were seen between the hypocellular and non-hypocellular AML groups in the complete remission rate (53.9% vs 61.3%, P = .139) or early death rate (defined as any death before 8 weeks; 14.7% vs 13.0%, P = .629). The OS and EFS did not differ between the hypocellular and non-hypocellular AML groups (median OS: 16 vs 23 months, P = .169; median EFS: 6 vs 9 months, P = .215). Hypocellular AML is more frequently observed in older-aged patients and have fewer FLT3-ITD and NPM1 mutation, but the clinical outcomes of hypocellular AML do not differ from those of non-hypocellular AML.

Mutational and Copy Number Profiling of Circulating Tumor DNA in Acute Myeloid Leukemia Using Targeted Next Generation Sequencing

The assessment of circulating tumor DNA (ctDNA), released by tumor cells undergoing apoptosis or necrosis, has established utility in solid tumors due to the advantage of a non-invasive "liquid biopsy" replacing multiple site-specific biopsies. However, its role in acute myeloid leukemia (AML) is uncertain, where a significant proportion of variants detected in the bone marrow (BM) may not be detected in ctDNA (Short, Blood Adv 2020). We have previously demonstrated the possibility of comprehensive genomic characterization of lymphoid malignancy from ctDNA using a single targeted next generation sequencing (NGS) hybridization-based panel (Blombery, BJH 2017). We aimed to assess the performance of this same genomic approach in ctDNA and to compare it against BM in AML. In addition, we aimed to assess the integration of a sensitive variant caller (Mutect2; Benjamin, bioRxiv 2019) to the bioinformatics suite in an attempt to improve low-level variant detection. Nineteen patients were identified from sequential patients with AML treated at our institutions where paired ctDNA and BM aspirate DNA were available. ctDNA was analyzed using a hybridization-based NGS panel targeting genes recurrently mutated in hematological malignancy followed by a suite of bioinformatics tools including HaplotypeCaller (GATK)/Mutect2 (GATK) for variant calling, CNSpector/CNSpectorX (Markham, Sci Reports 2019) for copy number variation (CNV) assessment and GRIDSS (Cameron, Genome Res 2017) for structural variant detection. The cohort clinical details are summarized in Table 1; none had documented extramedullary disease at time of collection. A total of 66 unique variants in 27 genes were detected, summarized in Figure 1. Median number of variants detected was 3 per patient sample, including NPM1 (n=6), IDH1/2 (n=4) and FLT3 point mutation (n=2). Three patient samples had FLT3-ITD detected by fragment length analysis; none were detected by the NGS panel in either ctDNA or BM. Variant allele frequency (VAF) from both compartments were highly correlated (R2 0.87). Higher VAFs in ctDNA were more commonly observed for kinase activating mutations (12/17 variants) and TP53 (5/6). Using HaplotypeCaller alone, 58 and 61 variants were detected in the BM and ctDNA, respectively. Of the 2 variants "specific" to the BM, both (IDH1 and NRAS) were called by Mutect2 in ctDNA and confirmed by visual inspection of sequence read alignments. Of the 5 variants "specific" to the ctDNA, 4 were detected in the BM at low VAF: CBL (n=2), KRAS and TET2. One discrepant case was patient #15 with prior breast cancer: KRAS G13D 21% in ctDNA but absent in the BM. Analysis by Mutect2 additionally detected 3 variants not called by HaplotypeCaller: NRAS and KIT in both ctDNA and BM, and TP53 P278R (VAF 6%) specific to the ctDNA in patient #9 with normal karyotype AML without history of prior malignancy. Overall, 3/5 variants in ctDNA and 6/6 in BM with low VAF were kinase activating mutations. We then performed genome-wide alignment of off-target reads to generate a low-resolution digital karyotype and CNV from ctDNA (Figure 2) which was compared with CNV and conventional karyotyping from BM. CNVs were detected in ctDNA in 10/11 patients with abnormal karyotype (Figure 1). Of these, 6/7 with non-complex abnormal karyotypes had consistent ctDNA CNVs including (i) 3 patients (#1, #10 and #15) with either rearranged/amplified KMT2A by FISH were all found to have gains at 11q23.3-qter, and (ii) 1 patient (#4) had 2 marker chromosomes of unknown origin on karyotyping which were resolved as additional copies of 4p using ctDNA sequencing. Although no CNVs were detected in all 8 patients with normal karyotype, analysis of B-allele frequency from ctDNA revealed one patient (#5) with copy neutral loss of heterozygosity (CN-LOH) in 7q (with a concurrent EZH2 mutation &amp;gt;95% VAF). In summary, we have demonstrated the ability to detect sequence variants, perform low-resolution digital karyotyping, CNV detection and CN-LOH detection from ctDNA in AML using a single hybridization based NGS assay. When using this approach, we show a high degree of concordance for both sequence variant and CNV detection, supporting the use of ctDNA as an alternative to BM (e.g. in cases of dry tap, hypocellular AML or failed karyotyping). Finally, using a sensitive variant caller, additional mutations were able to be detected in the ctDNA, the significance of which require evaluation in future studies. Disclosures Tiong: Amgen: Consultancy, Honoraria; Pfizer: Consultancy; Servier: Consultancy. Wilson:Illumina: Other: Illumina Diagnostic Genomics Scholarship. Bajel:Novartis: Honoraria; Astellas: Honoraria; Abbvie: Honoraria; Amgen: Honoraria, Speakers Bureau; Pfizer: Honoraria. Blombery:Invivoscribe: Honoraria; Novartis: Consultancy; Janssen: Honoraria; Amgen: Consultancy.

Clinical Characteristics and Treatment Outcome of Hypocellular Acute Myeloid Leukemia Based on WHO Classification

The hypocellular acute leukemia is very rare atypical leukemia with frequency of 5-7% among patients with acute leukemias. It mainly occurs in older patients and usually has a myeloid phenotype. It is still unclear whether the outcome of hypocellular acute myeloid leukemia is less favorable than adult acute myeloid leukemia with normal cellularity. We retrospectively analyzed all hypocellular acute myeloid leukemias which were treated in 16years period, between January 1998 and December 2014. There were 33 patients, 21 male and 12 female. The median age of the patients was 58.9years (ranging from 19 to 88years) and median cellularity of bone marrow was 16%. All patients presented with cytopenias with median white blood cell count 1.9 × 109/l, platelets 47.2 × 109/l and hemoglobin 85.9g/l. Nineteen patients were treated with standard 3 + 7 protocol (daunoblastin 45mg/m2 1, 3, 5days, cytosin-arabinozide 100mg/m2/12h for 7days), 5 patients with HDAC protocol and, 3 (9%) with low dose cytosin-arabinoside and in 6 (18.1%) patients only supportive therapy was applied. One patient died on 34day after treatment with HiDAC, 3 patients after treatment with 3 + 7 regimen in full doses on days 23, 35, and 58days. Complete remission was achieved in 20/33 (60.60%) patients, with median duration of 14months. Median overall survival (OS) of the entire cohort was 16months, and for the treated group 21months (range 5-67months). Median OS of patients treated with low dose cytosine-arabinoside was 6months. The advanced age (p = 0.009, KK = - 0.46, Log rank, p = 0.031) as well as therapy options (Log rank p < 0.0001) shows a significant correlation with OS. We report a cohort of patients with hypocellular acute myeloid leukemia who responded to standard induction chemotherapy as are in standard acute myeloid leukemia.

P1-128 - Retrospective analysis of the clinical outcome of hypocellular acute myeloid leukemia in a single institution

P1-128 - Retrospective analysis of the clinical outcome of hypocellular acute myeloid leukemia in a single institution

Dysplastic Changes and Proliferation Index in Acquired Aplastic Anemia Are Not Associated with Progression to MDS/AML - a Study of Bone Marrow in Children and Adults

Acquired Aplastic Anemia (AAA) is a rare disease which progresses to MDS / AML in up to 15% of cases. When this happens, hematopathologists are asked whether the diagnosis of hypocellular Myelodisplastic Syndrome (h-MDS) would not have been confused morphologically with aplastic anemia.This study aims to identify morphological/immunophenotypical (M/I) findings that could predict this adverse prognosis in adults and children (<19y) diagnosed as AAA and verify if those criteria match with the ones described in literature in adult h-MDS (Bennett JM, Orazi A. Diagnostic criteria to distinguish hypocellular acute myeloid leukemia from hypocellular myelodysplastic syndromes and aplastic anemia: recommendations for a standardized approach. Haematologica, 2009;94:264-9)¹ and, more recently, in pediatric MDS (Baumann I, Niemeyer CM, Bennett JM, et al. Childhood Myelodisplastic Syndrome. In: Swerdlow SH, Campo E, Harris NL, et al (Ed.). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Fourth Edition. Lyon: IARC Press, 2008:104-7)², contributing to the discussion of this "grey zone".We retrospectively analyzed 123 patients/bone marrow (BM) biopsies at the moment of AAA diagnosis at Clinical Hospital of São Paulo Medical School from 1993 to 2012. Diagnosis of AAA was carried out according to classical criteria (Marsh JCW. et al. Guidelines for the diagnosis and management of aplastic anaemia. British Journal of Haematology, 2009;147:43-70). Evolution to MDS or AML was considered in the presence of at least one of the findings: significant dysgranulopoiesis or dysmegakaryocytopoiesis, more than 15% ring sideroblasts, blasts in peripheral blood or more than 5% blasts in bone marrow smear and/or biopsy, or in the presence of monosomy or deletion of the long arm of chromosome 7 by cytogenetic analysis (FISH or karyotype) of the BM. All biopsies were submitted to morphological (see Table 1) and immunophenotypic (MPO, Glycophorin A, Factor VIII, CD34, CD117 and Ki-67) evaluation by two hematopathologists without previous knowledge nor about the evolution of the patients neither cytogenetic analysis results. Nominal qualitative variables were analyzed by using Fisher’s exact test to check significant disproportion between the groups. The ordinal qualitative variables were analyzed for differences between groups by Mann-Whitney test. The significance level was 5% (a = 0.05). The correlation between the overall cellularity values of the samples and their proliferative index was evaluated by nonparametric Spearman r test.Seventy three (59%) were male, median age 25,3 years (7 months to 76years), 42 belongs to the pediatric group and 81 to the adults group. Median follow-up was 5,1y (range, 1 month to 22,1 years). Twelve patients (9,7%) (6 in each group) progressed to MDS/AML.Evaluation of M/I parameters are presented in Table 1. Criteria described by Bennett and Orazi¹ suggestive of h-SMD evaluated in our study were marrow dysgranulopoiesis, marrow dysplasia of megakaryocytes and CD34-positive blast cells in the presence of at least one of the previous two. Criteria described by Baumann et al.² suggestive of childhood MDS evaluated in our study were marrow dysgranulopoiesis, clusters of at least 20 erythroid precursors (1), increased number of proerythroblasts (2), increased number of mitoses of the erythroid elements (3) (criteria counted if 1+2, 1+3 or 2+3 were observed) and marrow dysplasia of megakaryocytes.There was no statistically difference in M/I findings as well as the presence of Bennett and Orazi¹ criteria for MDS and Baumann et al.² criteria for childhood MDS among total population, adults and children who developed and did not develop MDS/AML. There was a statistically significant correlation between the overall cellularity values of the samples and their proliferative index.Adult and pediatric patients with AAA, including those that progress to MDS/AML, have similar M/I characteristics. Some changes described by Baumann for pediatric MDS are also found in pediatric and adults cases with AAA. In addition, the proliferative index may be increased in cases of AAA and this finding has no correlation with progression to MDS/AML. M/I changes in bone marrow biopsies in AAA have failed to identify a group at higher risk for progression to MDS/AML in our series. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Hypoplastic acute myeloid leukemia-M4: A rare case report

Hypocellular acute myeloid leukemia (AML) is defined as AML with bone marrow cellularity <20%. Hypocellular AML is an infrequent entity. Its frequency ranges between 5% and 12% of all cases of AML. Hypocellular variants of acute leukemia almost always have a myeloid phenotype and usually develop secondary to radiation or chemotherapy. We report a rare case of Hypocellular AML-M4 occurring in a 60-year-old woman who was incidentally found to be positive for HIV.

HAG regimen improves survival in adult patients with hypocellular acute myeloid leukemia.

BackgroundHypocellular acute myeloid leukemia (Hypo-AML) is a rare disease entity. Studies investigating the biological characteristics of hypo-AML have been largely lacking. We examined the clinical and biological characteristics, as well as treatment outcomes of hypo-AML in our institutes over a seven years period.Design and MethodsWe retrospectively analyzed data on 631 adult AML patients diagnosed according to the French-American-British (FAB) classification and WHO classification of tumors of haematopoietic and lymphoid tissue, including 43 patients with hypo-AML. Biological variables, treatment outcomes and follow-up data on hypo-AML patients were analyzed.ResultsOut of 631 AML patients, 47 (7.4%) were diagnosed as hypo-AML, out of which 43 patients were evaluable. Compared with non-hypocellular AML, hypo-AML patients tended to be older (P = 0.05), more likely to present with leukocytopenia (P < 0.01) and anterior hematological diseases (P = 0.02). The overall complete remission (CR) rate, disease free survival (DFS), and overall survival (OS) in hypo-AML patients were comparable to those in non-hypo AML patients. Twenty-seven (62.8%) patients with hypocellular AML were treated with the standard regimen of anthracyclines and cytarabine (XA) (associated CR rate: 51.9%; median OS: 7 months; median DFS: 6.5 months). Sixteen (37.2%) patients were treated with a priming regimen containing homoharringtonine, cytarabine and G-CSF (HAG) (associated CR rate: 81.25%; median OS: 16 months; median DFS: 16 months).ConclusionsThe overall prognosis of hypo-AML was not inferior to that of non-hypo AML. HAG regimen might increase response rates and improve survival in hypo-AML patients.

Hypocellular acute leukemia: study of clinical and hematological features

Hypocellular acute leukemia was previously referred to as smoldering leukemia. This is currently defined as having ≥20 % blasts in peripheral blood or bone marrow with cellularity of less than 20 % in bone marrow biopsy at presentation. Hypocellular variants of acute myeloid leukemia (AML) are commoner than that of acute lymphoid leukemia (ALL). They may pose a diagnostic challenge to the treating clinician and pathologist as they can simulate hypoplastic myelodysplastic syndrome and aplastic anemia. It is of utmost importance to distinguish these overlapping disorders as treatment modalities differ. Details of clinical features, complete blood counts, bone marrow aspirate findings, percentage cellularity, pattern of infiltration in trephine biopsies, and immunophenotyping by flow cytometry or immunohistochemistry were analyzed in cases diagnosed as hypocellular acute leukemia. Hypocellular acute leukemia constituted 2.5 % (8/316) of all diagnosed cases of acute leukemia during the study period. Seven of the eight cases of hypocellular acute leukemia were hypocellular AML while one was hypocellular ALL. Median age of patients was 45 years, with a male:female ratio of 1.7:1. Mean duration of symptoms was 1.2 months, with most common presenting feature being fever. None of the patients except one had an antecedent hematologic disorder or chemotherapy or radiotherapy. Hypocellular acute leukemia is important to recognize from other overlapping disorders. Clinical parameters and laboratory data including immunophenotyping can aid in distinguishing them.

Translocation (8;21) acute myeloid leukemia presenting as severe aplastic anemia

We report a case of t(8;21) acute myeloid leukemia presenting as severe aplastic anemia. While initial bone marrow biopsy lacked any cytogenetic abnormalities in 20 analyzed metaphases, repeat bone marrow biopsy eight days later demonstrated this translocation. Initial cytogenetic analysis of 20 metaphases was therefore insufficient to make the diagnosis of hypocellular acute myeloid leukemia. We discuss that further complementary molecular tests, such as CGH, would likely provide a more robust diagnosis of hematopoietic diseases.

Translocation (8;21) Presenting As Severe Aplastic Anemia

Translocation of 8;21 (q22;q22), generating a fusion of RUNX1 and AML1 genes is considered leukemia-defining and typically presents as an unequivocal acute myeloid leukemia (AML) with peripheral blood blasts and a hypercellular marrow, although it has been reported in patients with Fanconi anemia and myelodysplastic syndrome (MDS) (Quentin S et al. Blood 2011 Apr 14;117(15)). Aplastic anemia is a rare disease characterized by severe pancytopenia and a hypocellular marrow. A few cytogenetic abnormalities, namely trisomy 8 and monosomy 7, are associated with particularly refractory aplastic anemia, and monosomy 7 is associated with clonal evolution to MDS and rapid progression to AML. We describe a case of newly-acquired severe aplastic anemia in a 23 year old woman. Laboratory studies at presentation showed white blood cells 1.38 k/uL, absolute neutrophil count 0 k/uL, hemoglobin 7.4 g/dL, absolute reticulocyte count 5 k/uL, and platelets 38 k/uL. Bone marrow biopsy was 5% cellular with trilineage hematopoiesis and absolutely no dysplasia, even on repeated review. Initial cytogenetic analysis performed outside the NIH at presentation was normal. The patient was transferred to our institution and promptly received standard immunosuppressive therapy given the severity of neutropenia. However, a repeat bone marrow analysis performed immediately prior to immunosuppression showed t(8:21) (q22;q22) by standard cytogenetics in 3 out of 20 metaphases, with confirmation by fluorescence in situ hybridization (FISH). Blasts were not identified despite multiple repeat bone marrow aspirations utilizing immunohistochemistry and flow cytometry. Testing for Fanconi anemia was negative and leukocyte telomere length was normal for age. She remained severely pancytopenic and transfusion dependent for many months. Chemotherapy for AML was withheld given the severe pancytopenia and absence of blasts, and a search for a bone marrow transplant donor was initiated. Progression to frank leukemia with circulating blasts occurred 8 months following initial presentation, just prior to unrelated donor allogeneic stem cell transplantation. To our knowledge, this is the first reported case of acquired severe aplastic anemia, profound marrow hypocellularity, hypocellular MDS or hypocellular AML occurring in association with the t(8;21)(q22;q22).This unusual case prompted us to perform comparative genomic hybridization (CGH) using the single nucleotide polymorphism (SNP) based CytoScan high density microarrays on DNA from the patient's bone marrow mononuclear cells. We detected multiple, large regions of copy neutral loss of heterozygosity (also referred to as uniparental disomy) in the patient's marrow, ranging in size from 3 to 29 Mbp on multiple chromosomes. We hypothesized that the copy-neutral loss of heterozygosity observed in this case would not be present in other patients with acquired aplastic anemia at diagnosis or in normal controls. CGH did not demonstrate any large regions of copy neutral loss of heterozygosity in 10 patients with acquired severe aplastic anemia and normal cytogenetics at diagnosis, nor in 35 healthy controls. Emerging data show that SNP arrays can detect abundant copy neutral loss of heterozygosity amongst select hematologic malignancies and are associated with the duplication of oncogenic mutations. In our patient, copy neutral loss of heterozygosity possibly provided a second lesion, in addition to the RUNX1/AML1 abnormality, that facilitated initiation or progression to leukemia. These results suggest SNP based CGH arrays may be useful in distinguishing hypocellular AML from aplastic anemia and further studies utilizing this technology are warranted. Disclosures:No relevant conflicts of interest to declare.

Durable second complete remissions with oral melphalan in hypocellular Acute Myeloid Leukemia and Refractory Anemia with Excess Blast with normal karyotype relapsing after intensive chemotherapy

We treated six patients who had relapsed after intensive chemotherapy, presenting initially with AML or RAEB, a hypocellular marrow and normal karyotype, and who were deemed unsuitable for re-induction with intensive chemotherapy, with low dose oral melphalan. Three of six patients achieved complete hematological response with no significant toxicity and with a duration of 12, 8 and 3+ months respectively. These three patients had received only two prior courses of chemotherapy each, in contrast to non-responders who were more heavily pre-treated. Low dose melphalan is highly effective therapy for this rare subtype of AML/RAEB, even in relapsed disease with limited prior chemotherapy.

Successful Treatment of Childhood Hypocellular Acute Myeloid Leukemia

Hypocellular acute myeloid leukemia (AML) is extremely rare in childhood. We report on a 7-year-old girl with hypocellular AML who was treated successfully with granulocyte-colony stimulating factor (G-CSF) and combined chemotherapy. High-dose G-CSF induced complete remission and she subsequently received reduced intensity conditioning and unrelated cord blood transplantation; however, this resulted in early rejection. After a complete hematological recovery, she received 3 courses of combination chemotherapy oriented toward AML. She has remained in complete remission for over 1 year after the completion of the therapy. G-CSF effectively induced remission, and combination chemotherapy has been proven to be feasible for patients with childhood hypocellular AML.

Hypocellular acute myeloid leukemia in adults: analysis of the clinical outcome of 123 patients

The hypocellular variant of acute myeloid leukemia accounts for less than 10% of all cases of adult acute myeloid leukemia. It is defined by having less than 20 percent of cellular bone marrow in a biopsy at presentation. It is unclear in the literature whether the outcome of hypocellular acute myeloid leukemia differs from that of non-hypocellular acute myeloid leukemia. We retrospectively analyzed all the cases reported to be hypocellular acute myeloid leukemia between 2000 and 2009. A second pathology review was conducted and the diagnosis was confirmed in all cases. One hundred twenty-three (9%) patients were identified: patients with hypocellular acute myeloid leukemia were older than those with non-hypocellular acute myeloid leukemia (P=0.009) and more frequently presented with cytopenias (P<0.001). Forty-one patients with hypocellular acute myeloid leukemia had an antecedent hematologic disorder and 11 patients had received prior chemo-radiotherapy for non-hematopoietic neoplasms. On multivariate analysis, overall survival, remission duration and event-free survival were comparable to those of other patients with acute myeloid leukemia. The outcome of hypocellular acute myeloid leukemia does not differ from that of non-hypocellular acute myeloid leukemia.

Hypocellular acute myeloid leukemia with bone marrow necrosis in young patients: two case reports

IntroductionHypocellular variants of acute myeloid leukemia are very rare and almost always occur in old aged patients. In contrast, hypocellular acute lymphoblastic leukemia usually occurs in children.Case presentationWe report two Indian patients with hypocellular acute myeloid leukemia, a 32-year-old woman and a 13-year-old boy. Interestingly, one of the patients also showed bone marrow necrosis.ConclusionHypocellular acute myeloid leukemia is a rare entity and can affect young individuals. It can be considered as a rare cause of bone marrow necrosis.

Diagnostic criteria to distinguish hypocellular acute myeloid leukemia from hypocellular myelodysplastic syndromes and aplastic anemia: recommendations for a standardized approach

Members of the French-American-British Cooperative Leukemia Working Group met to review cases of aplastic anemia, hypocellular myelodysplastic syndrome and hypocellular acute myeloid leukemia. Criteria were proposed and modified following three workshops. Additional input was obtained from another hematopathologist with a special interest in bone marrow histology and immunohistochemistry. Guidelines were recommended based on the workshop results as well as additional studies including selective immunohistochemistry, flow cytometry and cytogenetics.

Acute Myeloid Leukemia with t(8;21)(q22;q22) (AML1/ETO) in a Patient with Marked Hypocellularity and Low Blasts Count

According to the World Health Organization (WHO) classification system, cases with t(8;21)(q22;q22) should be diagnosed as acute myeloid leukemia (AML) even with a blast count of less than 20 percent in blood or bone marrow. It is an uncommon manifestation, moreover hypocellularity is rarely observed in this subtype of leukemia. Here, we report a case of t(8;21) in a patient with marked hypocellularity of less than 5 percent and a blast count of less than 20 percent. This patient responded relatively well to chemotherapy. An allogeneic bone marrow transplantation was performed with good engraftment. This case suggests that hypocellular AML with a t(8;21) has as good a prognosis as hypercellular AML with t(8;21).

Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia.

The National Cancer Institute (NCI) sponsored a workshop to develop a set of standardized diagnostic and response criteria for acute myeloid leukemia (AML) clinical trials. The French-American-British (FAB) classification was retained for diagnosing AML, with the addition of patients with bone marrow morphologic features of a myelodysplastic syndrome and less than 30% bone marrow blasts, but with greater than or equal to 30% blasts in the peripheral blood. In this report, there are four important subgroups of AML not defined in the FAB classification that are discussed: undifferentiated acute leukemia, MO (AML lacking definitive myeloid differentiation by morphology or conventional cytochemistry but with ultrastructural or immunophenotypic evidence for AML), mixed lineage leukemia, and hypocellular AML. Definitions of response for clinical trials are presented to facilitate comparisons among different studies. Complete remission is considered the only response worth reporting in phase III trials, since lesser responses do not improve survival. Partial remissions may be of interest to identify active new agents in phase I and II studies. Monoclonal antibodies and cytogenetic studies are not part of the routine assessment of remission or reassessment at relapse, and their role in the evaluation of patients with AML is currently being evaluated in clinical trials. Although we recognize that some of the definitions in this report are arbitrary, generalized use of these guidelines will make results of clinical trials more comparable and interpretable.