Search

Objectives We attempt to analyze bone marrow findings and correlation with cytopenia(s) after anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell infusion in this study. Methods Relevant clinicopathologic data, including complete blood counts, neutrophil counts, relevant therapy history, and pre- and posttherapy bone marrow evaluations, were studied in 12 patients who received anti-BCMA CAR T-cell therapy. Results Bone marrow findings after CAR T-cell therapy were available in 6 of 12 cases, 3 of which showed markedly hypocellular marrow with either markedly reduced or essentially absent hematopoiesis. One case showed a hypocellular marrow with trilineage hematopoiesis, while the remaining 2 cases showed persistent involvement by plasma cell myeloma. Reticulin stains did not reveal significant fibrosis. Ten patients had anemia, and 8 patients had leukopenia and thrombocytopenia at day 90 posttherapy. Long-term follow-up showed persistent disease in 10 of 12 cases. Conclusions Prolonged cytopenias occur in most patients after BCMA CAR T-cell therapy with bone marrow evaluations demonstrating associated marked hypocellularity with minimal or no hematopoiesis without an increase in fibrosis. [ABSTRACT FROM AUTHOR]

Both hypocellular leukemia and Philadelphia (Ph) chromosome-positive mixed-phenotype acute leukemia (MPAL) are rare subtypes of leukemia showing unfavorable outcomes and lacking established optimal management. Ph-positive leukemia most often presents with hypercellularity and hypoplasia is a rare condition. The present study reports an extremely rare case of hypocellular biclonal Ph-positive MPAL, which was diagnosed by biopsy and genetic analysis of bone marrow, and successfully treated with dasatinib and steroids. Briefly, a 77-year-old man presented with pancytopenia and flow cytometry of bone marrow could not be evaluated due to hypocellularity. The patient was finally diagnosed with hypocellular Ph-positive MPAL by genetic analysis and immunostaining of bone marrow biopsy. Although blood cells recovered with methylprednisolone pulse administration alone for concurrent optic neuritis, hematopoietic function rapidly normalized with dasatinib administered after definitive diagnosis of Ph-positive leukemia. Dasatinib and oral prednisolone were continued following methylprednisolone pulse administration and the patient achieved molecular complete remission (CR) on day 140 of treatment; molecular CR was maintained thereafter without any severe adverse events. In conclusion, the combination of dasatinib and a steroid may be one of the tolerable treatment options for elderly patients with hypocellular biclonal Ph-positive MPAL. Furthermore, genetic analysis and immunostaining of bone marrow biopsy can help with the diagnosis of leukemia with hypocellular bone marrow. [ABSTRACT FROM AUTHOR]

Objectives: Hypocellular acute myeloid leukemia (AML) is uncommon. Despite the prognostic and therapeutic importance of mutational analysis, the mutational landscape of hypocellular AML is not well understood.Methods: We identified 25 patients with hypocellular AML, and 141 patients with nonhypocellular AML were identified as a control group. We applied next-generation sequencing for the first time to profile this entity.Results: The hypocellular AML patients were older than those with nonhypocellular AML (P = .037). At diagnosis, hypocellular AML had lower leukocyte counts (P = .012), higher hemoglobin (P = .003), and lower blast counts in the peripheral blood (P < .001) and bone marrow (P = .003). Hypocellular AML was less likely to have mutations involving cell proliferation (P = .027) and NPM1 (P = .022) compared with nonhypocellular AML. Hypocellular AML showed a high incidence of spliceosomal mutations and myelodysplastic syndrome-defining chromosome abnormalities (65%), but the incidence was not significantly different from that in nonhypocellular AML. There was no significant survival difference between hypocellular and nonhypocellular AML.Conclusions: To our knowledge, this study is the first to demonstrate hypocellular AML showed fewer genetic alterations involving cell proliferation and NPM1 when compared directly with nonhypocellular AML; this finding likely contributes to the low marrow cellularity in at least a portion of the patients with hypocellular AML. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia and predisposition to both hematologic malignancies and solid tumors. We report, a 14-yearold boy who presented with clinical features of aplastic anemia (AA). Subsequent bone marrow examination and multiparametric flowcytometric immunophenotyping revealed an evolving hypoplastic acute myeloid leukemia. Chromosomal breakage studies using clastogenic agent mitomycin C showed 88% stress induced chromosomal/chromatid breaks, gaps and rearrangements revealing an underlying FA. The case emphasizes upon the role of a systematic clinico-investigative approach in diagnosing such patients who by clinical criteria appear to have idiopathic AA and appear phenotypically normal. A timely and accurate diagnosis becomes vital in these cases to implement appropriate therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although most patients with myelodysplastic syndrome (MDS) exhibit bone marrow hypercellularity, a subset of them present with a hypocellular bone marrow. Specific factors associated with poor prognosis have not been investigated in patients with hypocellular MDS. METHODS: The authors studied a cohort of 253 patients with hypocellular MDS diagnosed at The University of Texas MD Anderson Cancer Center between 1993 and 2007 and a cohort of 1725 patients with hyper-/normocellular MDS diagnosed during the same time period. RESULTS: Patients with hypocellular MDS presented more frequently with thrombocytopenia ( P < .019), neutropenia ( P < .001), low serum β-2 microglobulin ( P < .001), increased transfusion dependency ( P < .001), and intermediate-2/high-risk disease (57% vs 42%, P = .02) compared with patients with hyper-/normocellular MDS. However, no difference in overall survival was observed between the 2 groups ( P = .28). Multivariate analysis identified poor performance status (Eastern Cooperative Oncology Group ≥2), low hemoglobin (<10 g/dL), unfavorable cytogenetics (−7/7q or complex), increased bone marrow blasts (≥5%), and high serum lactate dehydrogenase (>600 IU/L) as adverse independent factors for survival. CONCLUSIONS: A new prognostic model based on these factors was built that segregated patients into 3 distinct risk categories independent of International Prognostic Scoring System (IPSS) score. This model is independent from the IPSS, further refines IPSS-based prognostication, and may be used to develop of risk-adapted therapeutic approaches for patients with hypocellular MDS. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Hypocellular myelodysplastic syndrome (MDS) represents only a small portion of MDS, of which, the clinical significance has not been well-defined. By using currently accepted age-adjusted criteria to define hypocellularity as <30% in patients <70 years old, and <20% in >70 years old, we identified 163 (15.5%) hypocelluar MDS from 1049 consecutive adult MDS patients over an 11-year period (1995–2006). Compared to normal/hypercellular MDS, hypocellular MDS patients were younger (p <0.01), less anemic (p =0.02), but more neutropenic (p <0.001) and thrombocytopenic (p =0.05), and had a comparable cytogenetic risk group distribution (p =0.09) and international prognostic scores (IPSS, p =0.13). With a median follow-up of 52 months, hypocellular MDS showed a favorable overall survival (56 months versus 28 months, log-rank p <0.0001) over normal/hypocellular MDS, and this survival preference was also demonstrated in all IPSS groups and cytogenetic risk groups, and was independent of all other risk factors (Cox regression test, p =0.01). In conclusion, our study demonstrated that hypocellular MDS has characteristic clinicopathologic features, and bone marrow hypocellularity in MDS is an independent factor which predicts a favorable outcome. [Copyright &y& Elsevier]

Bone marrow (BM) histology of 102 myelodysplastic syndromes (MDS) patients was analyzed retrospectively. All the cases were reclassified according to the World Health Organization (WHO) classification. Karyotype study was conducted for all except one. Fifteen of the MDS cases were hypoplastic. The cellularity in bone marrow histology is sometimes ineffective in the differential diagnosis of MDS and aplastic anemia (AA). Nonetheless, a marked decrease in the number of megakaryocytes (average, 0.3/mm2; range, 0–2/mm2) even in the hyperplastic foci of the marrow of AA was the most important histological feature differentiating AA from MDS, whereas the number of megakaryocytes increased in most MDS cases (44/mm2; range, 1–240/mm2) and also in hypoplastic MDS (14/mm2; range, 8–26/mm2). Hyperplastic marrow had a significantly high frequency of progress to acute myeloid leukemia (AML) and hypoplastic MDS had a lower rate of progress to AML. Severe myelofibrosis had a significantly poor prognosis. An increase in CD34-positive cells in MDS indicated a high rate of progress to AML. As for the patients with refractory cytopenia with multilineage dysplasia (RCMD; the new category under the WHO classification), the increased number of megakaryocytes was correlated with poor prognosis. [ABSTRACT FROM AUTHOR]

The article is concerned with incidence, clinical features, response to therapy, and prognosis of patients with hypocellular myelodysplastic syndromes. Bone marrow (BM) cellularity <30% (or <20% in patients >70 yr) was found in 24 of 236 (10.2%) trephine biopsies. Median age was 61 yr, with significant male predominance (M/F=3.0) At diagnosis, median hemoglobin was 83 g/L, median platelet and neutrofil counts were 31 × 109/L and 1.2 × 109/L, respectively. According to FAB classification, 17 patients had RA, 6 had RAEB, and only 1 had RAEB-t. Beside marrow hypoplasia, the most prominent PH finding was megakaryocyte hypoplasia and dysplasia, found in two-thirds of cases, each. Comparison between hypocellular and normo/hypercellular MDS cases regarding clinicopathological features showed younger age, more severe cytopenia, less blood and BM blast infiltration, MK hypoproliferation, and more pronounced stromal reactions in former cases. Karyotypic abnormalities were present in 12.5% hypocellular cases, in contrast to 44.6% normo/hypercellular cases ( p=0.0025). Eleven patients were treated with supportive therapy alone, six with danazol or androgens, six with immunosuppressive therapy, and one with LDARAC. However, complete or partial response was achieved in only four patients treated with danazol or androgens. None of the patients developed leukemia. Eleven patients died, so marrow insufficiency was the main cause of death. Median survival was 33 mo for hypocellular MDS, and 19 mo for normo/hypercellular MDS ( p=0.09). The results confirm the existence of hypocellular variant of MDS, which seems to have better prognosis than those patients with normo/hypercellular disease. [ABSTRACT FROM AUTHOR]

Primary myelodysplastic syndrome (MDS) with myelofibrosis is a rare hematological disorder that should be classified as a distinct subgroup of MDS. Treatment of MDS with myelofibrosis remains problematic and the prognosis is poor in these patients, particularly following transformation into acute myeloid leukemia (AML). The current study presents the case of a 28-year-old male diagnosed with MDS associated with myelofibrosis, together with hypocellular bone marrow features. Following induction chemotherapy consisting of mitoxantrone and cytarabine, the patient achieved complete remission, but developed severe myelofibrosis. The patient relapsed and the disease transformed into AML 12 months later. However, the extent of the myelofibrosis was markedly alleviated upon administration of a FLAG regimen that consisted of fludarabine, cytarabine and granulocyte colony-stimulating factor during the AML transformation. After one course of the FLAG regimen, the patient achieved a second complete remission. As there was no suitable donor for hematopoietic stem cell transplantation (HSCT), the patient relapsed and succumbed shortly after. In conclusion, MDS with fibrosis is an aggressive disease, but the degree of myelofibrosis may not be associated with the progression of hypocellular MDS, and allogeneic HSCT remains a potentially curative option for affected patients. [ABSTRACT FROM AUTHOR]

We describe a patient with bone marrow hemophagocytosis who had classic dengue fever associated with nasal bleeding and pancytopenia. The patient recovered with appropriate supportive care. A literature search shows fewer than 20 case reports of dengue related hemophagocytosis in the English literature. Our patient is an interesting case of dengue related hemophagocytic syndrome and adds an additional case to the literature. Clinicians should consider that the occurrence of hemophagocytosis in the appropriate geographical area could be due to dengue virus infection and present with pancytopenia. [ABSTRACT FROM AUTHOR]

Background: Induction chemotherapy for acute myeloid leukemia (AML) is based on the "7+3" cytarabine/anthracycline regimen. A nonhypocellular day 14 (D14) bone marrow sample with a blast count > 5% to 10% is suggestive of residual leukemia, for which a second course of induction chemotherapy has been recommended. Although the prognostic value of D14 bone marrow findings has been established, its use as a decision point is controversial because the benefit of repeat induction has been questioned., Patients and Methods: In the present single-center retrospective study of 113 patients with newly diagnosed AML, we evaluated the role of cellularity on the clinical outcomes of patients with residual morphologic leukemia (blasts ≥ 5%). Among 64 patients with D14 bone marrow samples, 31 had residual morphologic leukemia., Results: The complete remission (CR) rates were greater for the hypocellular (11 of 16) than for the nonhypocellular (4 of 15) patients (P = .03). The median overall survival (OS) for the hypocellular D14 patients was longer than that for the nonhypocellular patients (17 vs. 8 months; P = .02). No significant difference between the receipt of reinduction therapy and CR or OS was found on logistic or survival model analysis. The specificity for residual leukemia on D14 bone marrow samples was better for cellularity ≥ 20% and blasts ≥ 20% than for blasts ≥ 5%., Conclusion: The results of our study have shown that patients with < 20% cellularity and < 20% blasts on the D14 bone marrow assessment should continue observation until recovery rather than receive additional immediate therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Calcifying fibrous tumor (CFT) is a rare benign mesenchymal lesion known to arise at multiple body sites that may clinically mimic other more aggressive lesions in the gastrointestinal (GI) tract. In this study we describe the clinicopathologic findings of 28 GI tract CFTs. Tumors predominantly arose in middle-aged adults with a slight female predominance. The most commonly involved sites were small bowel and colon, followed by stomach and appendix. Tumors ranged from 0.3 to 9.3 cm (median 1.4 cm), and submucosa was the most commonly involved layer. All tumors were well circumscribed and unencapsulated. Microscopically, tumors were hypocellular and composed of spindle cells with abundant, haphazardly arranged hyalinized collagen. No necrosis and less than one mitosis per 10 HPF were identified in all cases. Calcification was present in most (81%) of the cases. All cases had lymphoplasmacytic inflammatory infiltrates either scattered throughout the lesion with occasional perivascular conglomeration or in the form of lymphoid aggregates. A lymphoplasmacytic cuff was usually present (81%). Immunostains showed variable CD34 immunoreactivity and variable numbers of IgG4-positive plasma cells. The lesional cells were negative for DOG-1, ALK-1, S100, C-kit, Sox10, Melan A, HMB45, desmin, CK7, and CK20, and showed cytoplasmic staining for β-catenin. Follow-up information was available in 5 cases with no recurrences reported to date (mean follow-up, 3 years). CFT is a rare benign tumor that can occur in part of the GI tract and should be distinguished from other mesenchymal tumors due to its low risk of recurrence., (Copyright © 2017 Elsevier Inc. All rights reserved.)