Acute Panmyelosis With Myelofibrosis Research Articles

Acute panmylelosis with myelofibrosis - A rare case report with review of literature.

Acute panmyelosis with myelofibrosis (APMF) corresponds to <1% cases of acute myeloid leukemia, which could be an underestimation due to missed diagnosis. Due to its rapidly fatal course, it warrants a timely and correct diagnosis. We present a case of a 44-year male who came with a short history of fever, generalised weakness, revealed pancytopenia with occasional circulating blast in the peripheral blood smear. Bone marrow aspirate was dry tap,biopsy revealed panmyelosis with myelofibrosis with increased (22%) blasts. Flowcytometric immunophenotyping, cytogenetics and molecular tests were undertaken. Together with clinical details, immunophenotypic profile, cytogenetics and molecular studies, the diagnosis of Acute panmyelosis with myelofibrosis was made and managed accordingly. 32 The WHO 2017 describes APMF as an acute panmyeloid proliferation with increased blasts (≥20% in the bone marrow or peripheral blood) and accompanying marrow fibrosis. APMF is rare with poor prognosis thus, must be differentiated especially from Acute megakaryoblastic leukemia to arrive at the correct diagnosis which will help reduce/prevent the early mortality by providing timely chemotherapy followed by upfront hemopoietic stem cell transplantation.

Acute Panmyelosis with Myelofibrosis in an Elderly Patient- an Uncommon Cause of Pancytopenia

Introduction: Acute panmyelosis with myelofibrosis (APMF) is rare yet a fatal hematological malignancy. It had been classified as a subtype of acute myeloid leukemia (AML) under the category "AML, not otherwise specified" in the WHO classification of hematological tumors. APMF usually presents with cytopenia without any marked splenomegaly. We report a case of an 80-year-old female who presented with generalized weakness. An extensive workup unmasked the presence of acute panmyelosis with myelofibrosis. Case Report: An 80-year-old female patient with history of epilepsy, essential hypertension, and hyperlipidemia presented to the clinic for generalized weakness and confusion for two weeks. She was also having dyspnea, initially on exertion, which progressed to even at rest for the last one week and was unable to ambulate without assistance. The patient also reported easy bruising with minor trauma and bruises on the upper extremity. The patient denied having any fever, chills, chest pain, orthopnea, dizziness, loss of consciousness, history of bleeding, or weight loss. On physical examination, the patient did not have enlarged lymph nodes or hepatosplenomegaly. Initial labs showed hemoglobin of 4.8 g/dL, platelets 5K/uL, a white blood count of 1.8 K/uL with differentials of 49% segmented neutrophils, 0.85 K/uL absolute neutrophils, 4% band cells, 44% lymphocytes, 1% myelocytes, 1% nucleated RBC's, 0.09 K/uL absolute monocytes, and 3% monocytes. Her absolute reticulocyte count was 0. Red blood cells were hypochromic with anisopoikilocytosis. The coagulation profile showed PT 16.5 seconds, INR 1.4, and aPTT 37 seconds. She also underwent a CT head for the confusion which was unremarkable. Chest x-ray revealed left mid & lower zone infiltrates consistent with pneumonia and the patient was given ceftriaxone. The patient was transfused irradiated packed red blood cells. There was a concern for bone marrow disorders such as myelodysplastic syndrome and leukemia, so the patient underwent a bone marrow biopsy. Flow cytometry of bone marrow aspirate revealed no significant blast cells; however, it showed myeloid neoplasm with myelofibrosis and proliferation of the atypical megakaryocytes with variable hypercellularity and diffusely marked reticulin fibrosis. Immunohistochemistry was positive for E-cadherin on megaloblastic erythroid, myeloperoxidase (highlighted patchy foci of maturing myeloid cells), CD34 (widespread positive in the atypical megakaryocyte, but not blast cells), and CD61 (GPIIIA). These findings along with the absence of splenomegaly were consistent with Panmyelosis with myelofibrosis. After the family discussion about chemotherapy and bone marrow transplant, a combined decision was made for hospice with comfort measures and the patient died within a week. Discussion: Acute panmyelosis with myelofibrosis is not thoroughly studied. Although WHO has classified it as a type of AML, some still consider it equivalent to AMKL or an acute kind of MDS (myelodysplastic syndrome). APMF comprises less than 1% of the cases of AML. The disease typically presents with an acute onset of pancytopenia without any splenomegaly and is rapidly fatal with mean survival of less than a year. Significant differential diagnoses include acute megakaryoblastic leukemia (AML) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). AML and APMF share multiple features like fibrotic un-aspirable bone marrow and the presence of megakaryoblasts. However, in AML, most of the blast population comprises megakaryoblasts, while in APMF, non-megakaryocytic cells are predominant. Compared to AML-MRC, abrupt clinical onset and worse survival rate point towards APMF. In addition, multilineage dysplasia led by myelodysplastic syndrome is also characteristic of AML-MRC. Similarly, exposure to leukemogenic therapeutic agents should also be ruled out, as such cases should be categorized as MDS or AML therapy-related diseases. Due to the disease being extremely rare, there are no established management protocols. The most commonly used treatment is with 3 + 7 induction chemotherapy. A retrospective study showed a poor outcome of hematopoietic cell transplantation due to a high relapse rate. Another case showed remission by 3+7 induction with idarubicin and cytarabine followed by cytosine arabinoside. In our case, hospice care was preferred considering the age and comorbidities

A population-based study of acute panmyelosis with myelofibrosis in the United States: 2004 to 2015.

e19003 Background: Acute panmyelosis with myelofibrosis (APMF) is a rare subtype of acute myeloid leukemia characterized by acute panmyeloid proliferation with increased blasts, cytopenias with bone marrow fibrosis, and absence of splenomegaly. There is a paucity of population-based studies of APMF. Methods: We queried the United States Surveillance, Epidemiology, and End Results (SEER) database and National Cancer Database (NCDB) using the ICD-O-3 code 9931/3. The SEER 17 registries (2004-2015) were used to find data on incidence. For NCDB data, comorbid disease burden was calculated using the Charlson-Deyo Score (CDS). Hazard ratios (HR) with confidence intervals (CI) were calculated using a Cox proportional hazards model. Overall survival (OS) was estimated with the Kaplan-Meier method. Variables significant in univariable analysis were included in a multivariable analysis. Results: We identified 260 APMF patients using the SEER database. Incidence was 0.3 cases/million individuals and did not change significantly from 2004-2015. With a median follow up of 6.9 years (95% CI 6.1-7.8), the median OS was 2.3 years (95% CI 1.7-2.8). We identified 530 APMF patients using the NCDB. The median age at diagnosis was 67 years (range 22-90) and 311 (59%) were male. With a median follow up of 5.0 years (95% CI 3.0-7.6), the median OS was 2.3 years (95% CI: 0.8-6.5). OS was 69%, 31%, and 18% at 1-, 5-, and 10- years, respectively. Patients diagnosed in 2012-2015 had a significantly improved OS compared to those diagnosed in 2004-2007 (HR 0.65, 95% CI 0.49-0.85; p=0.002). 271 patients (53%) patients received chemotherapy. The OS for those that received chemotherapy was 70% at 1 year and 30% at 5 years versus 70% and 32% at 1- and 5- years for those who did not ( p=0.99). The median time to chemotherapy from time of diagnosis was 25 days (range 0-532 days). 52 patients (10%) underwent transplantation and the OS of those patients was 90% at 1 year and 45% at 5 years versus 67% and 29% at 1- and 5- years for those who did not (HR: 1.7 (95% CI: 1.2-2.6), p=0.006). In univariable analysis, factors predicting inferior OS were age ≥ 65 years old at diagnosis (HR 1.8, 95% CI 1.5-2.3; p&lt;0.001), male sex (HR 1.5, 95% CI 1.2-1.8; p&lt;0.001), CDS ≥ 1 (HR: 1.5 (95% CI: 1.2-2.0), p&lt;0.001), government insurance (HR 1.8, 95% CI 1.4-2.3; p&lt;0.001), diagnosis at a non-academic facility (HR 1.6, 95% CI 1.2-2.0, p&lt;0.001), and not receiving a hematologic transplant (HR 1.7, 95% CI 1.2-2.6; p=0.006). Multivariable-adjusted analysis is shown in the Table. Conclusions: The overall incidence of APMF has not changed between 2004 and 2015, but OS for 2012-2015 was improved compared to 2004-2007. Age ≥ 65 years old, male sex, CDS ≥ 1, and diagnosis at a nonacademic facility predicted inferior OS. Multivariable-adjusted analysis.[Table: see text]

Acute Panmyelosis with Myelofibrosis: A Rare Subtype of Acute Myeloid Leukemia

Acute panmyelosis with myelofibrosis (APMF) is a subtype of acute myeloid leukemia (AML) classified among the category of “AML, not otherwise specified” in the WHO 2016 classification of hematopoietic tumors. It is a rare, fatal hematological neoplasm that is characterized by acute onset of cytopenias and bone marrow fibrosis in the absence of splenomegaly or fibrosis related morphological changes in the red blood cells. The difficulty of diagnosis and management explains why APMF is rarely reported in Africa. We report here the case of a 30-year-old man who presented with dizziness, palpitations and dyspnea. Diagnosis of APMF was retained on bone marrow histology and immunohistochemistry which showed bone marrow fibrosis and high cellularity with majority of myeloid blast cells. The patient was treated by low dose cytarabine monotherapy 30 mg/m2 per week. At 3 months of treatment, the patient was transfusion-independent, with normalization of hemoglobin and platelets counts. However, the death occurred after 8 months. This case highlights the diagnosis specificity and management of AMPF, knowing the number of potential differential diagnoses and difficulties of its therapeutic management.

Abstract B03: Acute megakaryoblastic leukemia is associated with poor overall survival and enriched in JAK2 variants

Abstract In this study, we aimed to characterize the molecular mechanisms of two very rare subtypes of AML: acute megakaryoblastic leukemia (AMKL) and acute panmyelosis with myelofibrosis (APMF). Our goal is to describe the clinical-pathologic features of APMF and explore the genomic landscape AMKL to further understand these rare malignancies. We identified 35 patients diagnosed with AMKL (n=27) and APMF (n=8) at Mayo Clinic between 1995 and 2015 by retrospective chart review. For 10 of the AMKL patients, tissue was available for whole-exome sequencing and was analyzed in comparison to a published AML reference population. The median overall survival was shorter in patients with AMKL (3.9 months, 95% CI 1.7-7.4) than in patients with APMF (14.3 months, 95% CI 0.7-NE, p = 0.026,). For both AMKL and APMF, patients who underwent allogeneic hematopoietic stem cell transplantation had better overall survival (14.3 months, 95% CI 1.9-NE) compared to those not undergoing transplantation (4.6 months, 95% CI 1.5-7.4, p = 0.003). Patients with AMKL presented more frequently with splenomegaly, with higher peripheral blood blast counts, and with higher serum lactate dehydrogenase concentrations. 9 out of 10 AMKL patients with available tissue for sequencing demonstrated variants in 22 of 35 AML driver genes, with JAK2 V617F as the most common mutation. Although our small study numbers preclude firm conclusions, it does reflect the rarity of these AML subtypes. Furthermore, inferior survival in AMKL (compared to APMF) was reflected in its proliferative disease features such as splenomegaly, high blast counts, and high lactate dehydrogenase. Interestingly, the presence of JAK2 V617F variants in 40% of the interrogated samples was higher than expected. Although JAK2 is a known molecular driver in myeloproliferative neoplasms, it is actually very rare in de novo AML (~1%). Despite improved survival with allogeneic stem cell transplant, we can conclude that treatment outcomes for AMKL and APMF with standard-of-care therapy were sobering and that patients with these rare AML subtypes should undergo molecular evaluation to qualify them for clinical trials with novel targeted therapies. Citation Format: Marissa Li, Moritz Binder, Basma Basha, Ben Zhang, Alejandro Ferrer, Yuanhan Liu, Mrinal Patnaik, David Viswanatha, Naseema Gangat. Acute megakaryoblastic leukemia is associated with poor overall survival and enriched in JAK2 variants [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B03.

Hematopoietic Cell Transplantation for Acute Panmyelosis with Myelofibrosis: A Retrospective Study in Japan

Acute panmyelosis with myelofibrosis (APMF) is a rare subtype of acute myeloid leukemia characterized by acute onset of cytopenias and bone marrow fibrosis in the absence of splenomegaly. Because the prognosis of APMF is extremely poor even after chemotherapy, hematopoietic cell transplantation (HCT) has been used to treat APMF. However, the outcome after HCT for APMF remains unclear. To evaluate the outcomes and prognostic factors after HCT as a therapeutic modality for APMF, we retrospectively analyzed the Japanese registration data of 40 APMF patients who received allogeneic and syngeneic HCT between 2005 and 2015. The median age at HCT was 53.5 years (range, 16 to 70). The disease status at HCT was first complete remission (CR1) in 13 patients (33%). The probability of overall survival and the cumulative incidence of relapse at 3 years were 24% and 59%, respectively. Univariate analysis identified that female sex and disease status CR1 at the time of HCT were significantly associated with higher overall survival. Although APMF patients have a poor long-term prognosis even after syngeneic and allogeneic HCT, these data suggested that allogeneic HCT offered a curative option for APMF.

CALR, JAK2, and MPL mutation profiles in patients with four different subtypes of myeloproliferative neoplasms: primary myelofibrosis, essential thrombocythemia, polycythemia vera, and myeloproliferative neoplasm, unclassifiable.

We investigated mutation profiles of CALR, JAK2, and MPL in 199 Korean patients with myeloproliferative neoplasms (MPNs). In total, 199 patients with MPN (54 primary myelofibrosis [PMF], 79 essential thrombocythemia [ET], 58 polycythemia vera [PV], and eight MPN-unclassifiable [MPN-U]) and 4 patients with acute panmyelosis with myelofibrosis (APMF) were retrospectively subjected to Sanger sequencing for CALR, JAK2, and MPL. The overall frequency of CALR mutations was 12.6% (type 1 mutation, 16 patients; type 2 mutation, nine patients): most frequent in MPN-U (37.5%), followed by ET (17.7%) and PMF (14.8%). CALR mutations were not found in PV or APMF. CALR and JAK2 or MPL mutations were mutually exclusive. In PMF, the CALR mutations were associated with lower levels of leukocytes, lower bone marrow cellularity, and higher number of megakaryocytes. Patients with CALR-mutated ET more frequently progressed to the accelerated or blast phases compared with patients with JAK2 mutations. CALR mutations were frequently observed in the JAK2-negative MPNs, most frequently in MPN-U. The prognostic significance of CALR mutations likely differs among the MPN subtypes.

Acute Panmyelosis with Myelofibrosis - A Rare Subtype of Acute Myeloid Leukemia

One case of acute panmyelosis with myelofibrosis (APMF) is here reported. A 45 year old male presented with abrupt onset of rapidly progressing low backache, weakness and pancytopenia. On examination there was no organomegaly. Peripheral blood examination revealed normocytic normochromic red blood cells with 10% circulating blasts. Flowcytometric examination of peripheral blood revealed blasts which were positive for CD34, HLA− DR and myeloid associated antigens (i.e. CD13 and CD33). Blasts were negative for anti MPO. Bone marrow aspirate resulted in a dry tap. Bone marrow biopsy revealed panmyeloid proliferation with scattered blasts which were CD34 positive on imunohistochemistry and negative for anti MPO. Reticulin stain showed grade III myelofibrosis (WHO). Differential diagnosis considered included AML-M7, MDS-RAEB II and AML with myelodysplasia. He was started on chemotherapy [idarubicin and cytarabine; 3+7 induction regimen followed by three cycles of HIDAC (High dose cytosine arabinoside)] after which patient was in complete morphological remission with markedly reduced bone marrow fibrosis. He is now being worked up for allogeneic stem cell transplantation. Patient is asymptomatic at eight months of diagnosis. In conclusion these patients should be managed aggressively with AML therapy and this case report reaffirms the fact that APMF is subtype of AML.

Differential diagnosis of myelofibrosis based on WHO 2008 criteria: Acute panmyelosis with myelofibrosis, acute megakaryoblastic leukemia with myelofibrosis, primary myelofibrosis and myelodysplastic syndrome with myelofibrosis

The aim of this study was to characterize clinicopathological features of acute panmyelosis with myelofibrosis (APMF), acute megakaryoblastic leukemia with myelofibrosis (AMKL-MF), primary myelofibrosis (PMF) and myelodysplastic syndrome with myelofibrosis (MDS-MF) in order to provide the keys to the differential diagnosis of bone marrow (BM) fibrosis. We compared age, gender, splenomegaly, serum lactate dehydrogenase level, blood cell counts, blast counts in peripheral blood (PB) and BM, megakaryocyte counts, BM cellularity, dysplasia, and the karyotypes of patients with APMF (n=6), AMKL-MF (n=7), PMF (n=44), and MDS-MF (n=44). APMF showed hyperplasia of all three lineages, increase in megakaryocyte count with dysplasia and frequent abnormal karyotypes. AMKL-MF was associated with elevated BM blast counts, decreased BM megakaryocyte count with rare megakaryocytic dysplasia and chromosome 21 abnormality. PMF patients displayed splenomegaly, rare blasts in PB/BM, and JAK2 V617F mutation. MDS-MF patients showed pancytopenia, dysplasia in all three lineages and recurrent chromosomal abnormalities involving chromosome 5,7,12, and 17. Although differential diagnosis among APMF, AMKL-MF, PMF, and MDS-MF is very challenging due to the overlapping clinical and morphological features, meticulous investigation of the patient with respect to splenomegaly, blood cell count, PB and BM findings, and karyotype will serve as a guide to correct diagnosis.

Circulating Megakaryocyte-Derived Cells Detected by Flow Cytometry As Marker of Aggressive Neoplasms of Megakaryocytic Lineage in Acute Megakaryoblastic Leukemia and Allied Malignancies Presenting As Primary Myelofibrosis

AbstractAbstract 1461▪▪This icon denotes a clinically relevant abstractThe differential diagnosis of myelofibrotic disorders encompasses chronic primary myelofibrosis (PMF), myelodysplastic syndromes with fibrosis (MDS-F), acute panmyelosis with myelofibrosis (APMF) and acute megakaryoblastic leukemia (AMKL). Most of these conditions are recognized as distinct entities by the WHO 2008 revised classification of myeloid neoplasms; however, the WHO admits that often a definitive diagnosis is problematic, mostly because of specimens with insufficient cellularity (e.g., “dry tap”). Nevertheless, the correct identification of the most aggressive fibrotic disorders (APMF and AMKL) remains crucial, given their poor prognosis and subsequent need of intensive treatment (including transplantation). Even the most recent molecular studies did not result in any contribution in the differential diagnosis. Here we report our experience on a cohort of about 300 patients who were admitted in our bone marrow failure unit because of cytopenia in the last 7 years. All these patients were evaluated by standard peripheral blood and bone marrow cytology, karyotype analysis and bone marrow thephine biopsy, aiming to a definitive hematological diagnosis. Flow cytometry analysis was performed at initial presentation and then serially during the follow up on both peripheral blood and bone marrow aspirate. All patients were classified according to the WHO 2008 revised classification of myeloid neoplasms, and received the best standard treatment based on the specific disease, age and comorbidities. This report focuses on 8 patients who shared a unique flow cytometry finding of an aberrant megakaryocyte-derived cell population, which seems associated with a distinct disease evolution. Two of these patients received the diagnosis of AMKL according to bone marrow aspirate and trephine biopsy; the karyotype was complex in one case (monosomal karyotype, including a 5q-), whereas no Jak-2 mutation or any other genetic lesions could be demonstrated. Their blast cells were CD34+, CD38+, CD45+, CD117+, CD33+, CD13+; in addition, in the peripheral blood, we detected the presence of an aberrant cell population which was CD45-, CD42b+ (CD34+ in one case and CD34- in the other one). In the blood smear, we observed megakaryocyte fragments which likely correspond to this aberrant cell population, as identified by flow cytometry. Other three patients presented with a severe pancytopenia: all of them had a dry tap, and their trephine biopsies documented a massive fibrosis. They had no previous hematological disorder (one suffered from Behcet syndrome), normal karyotype and absence of any typical genetic lesion (i.e., wild-type Jak-2). All of them did not show splenomegaly, increased LDH or leukoerythroblastosis; their peripheral blood smear showed abnormal giant platelets, often resembling megakaryocyte fragments. Flow cytometry documented in the peripheral blood the presence of a distinct population of CD45-, CD42b+, CD61+ cells, which was also CD34+ in one case. These 3 patients were initially classified as PMF, even if APMF could not be ruled out; however, within 6 months they all progressed to AMKL. At this stage, typical CD34+, CD45+ blast cells were accompanied by a progressive increase of CD45+, CD42b+, CD61+ cells. This aberrant megakaryocyte-derived cell population (which could not be demonstrated in patients with thrombocytopenia) was also identified in 3 additional patients, who have a previous history of hematologic disorders: two had a history of pure red cell aplasia (successfully treated by immunosuppressive therapy), and one a 5q- melodysplastic syndrome (responding to lenalidomide, even with transient cytogenetic remission). In all of them we observed the appearance of CD45-, CD42b+ cells in the peripheral blood, which appeared as giant platelets/megakaryocyte fragments in the blood film; this finding within a few weeks was followed by progression to AMKL (5q- was detected in 2 of 3 cases). In conclusion, we demonstrate that aberrant circulating megakaryocyte-derived cells detected by flow cytometry may be useful in the differential diagnosis of myelofibrotic disorders. These giant platelets or megakaryocyte fragments, regardless the initial diagnosis, were associated with early evolution into AMKL, likely representing a surrogate marker for aggressive neoplasms of the megakaryocytic lineage. Disclosures:Risitano:Alexion: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Acute Panmyelosis with Myelofibrosis: An Evaluation of Distinctive Clinicopathological Features Including Bone Marrow Stroma.

Acute panmyelosis with myelofibrosis (APMF) is a rare AML category of the current WHO-classification. The main clinical characteristics are an acute onset of disease, no splenomegaly, few blasts in the blood and an aggressive clinical course. Differentiation of APMF from hyperfibrotic high-grade myelodysplastic syndromes with excess blasts or acute megakaryoblastic leukaemia may be difficult because of the actual lack of molecular markers. As a consequence of myelofibrosis and dry tap, bone marrow cytology and cytogenetic analyses are only available in a minority of cases. Therefore, histopathology and immunohistochemistry of trephine bone marrow biopsies may offer further clues to the biology of APMF.Our study focused on the clinicopathological features of 52 patients meeting the criteria of APMF. Cases with any other category of MDS or AML, a history of preceding chronic myeloproliferative disorder, especially idiopathic myelofibrosis, autoimmune disorders, and cytotoxic or radiation therapy were excluded. All patients presented with anemia, granulocytopenia, low to normal platelets and low peripheral blast counts (≤5%). Cytogenetic abnormalities included monosomy 7, del (7p), del (17p) and trisomy 8 or complex karyotypic abnomalities. The median survival was <12 months. The lethal outcome was due to severe pancytopenia or overt leukaemia. Multilineage maturation defects associated with a strikingly increased atypical megakaryopoiesis and slight to marked degrees of fibrosis were the characteristic features common to all bone marrow trephines. Abnormalities of megakaryocytes included loose grouping or prominent clusters of medium sized to small cells with nuclear hypolobulation and dwarf cells and occasionally scattered bizarre forms. By confocal laser scanning microscopy (CLSM) we observed heterogeneous megakaryocyte c-Mpl signals using a polyclonal rabbit antibody kindly provided by Dr. J. Spivak, Baltimore, MG, USA.Cytoplasmic immunolabeling ranged from weak in larger polymorphous forms to moderate or strong in smaller megakaryocytes. The predominantly membraneous c-Mpl localization of normal megakaryocytes was generally downregulated.In contrast to acute megakaryoblastic leukaemia, blasts rarely expressed CD61 or CD41, but predominantly myeloid or myelomonocytic antigens. In accordance with the data recently published by Orazi et al. (Mod Pathol 2005; 18: 603–14) blasts were less numerous than in acute megakaryoblastic leukaemia. Bone marrow stroma contained increased microvessels, CD4 and CD8+ T-cell subsets, B-cell rich lymphoid nodules and CD68+ macrophages. By CLSM, myofibroblastic cells coexpressing alpha-smooth muscle actin and cellular retinol-binding protein 1, a key molecule of retinoid metabolism, could be visualized ín the stromal compartment.In conclusion, refined in situ imaging techniques of bone marrow trephines improve the diagnostic impact of the WHO criteria for the diagnosis of APMF. Our study provides further evidence that both hematopoietic and stromal components of the bone marrow are conspicuously modulated in this uncommon disorder in keeping with the designation as a panmyelosis.

Acute panmyelosis with myelofibrosis: a clinicopathological study on 46 patients including histochemistry of bone marrow biopsies and follow-up.

Controversy continues whether acute panmyelosis with myelofibrosis (APMF) exists as a well-defined clinicopathological entity. Following exclusion of overt acute myeloid leukemia (AML), especially the megakaryoblastic subtype, a retrospective study was performed on 46 patients with clinical and morphological features suggesting the diagnosis of APMF. All patients had a bone marrow (BM) biopsy performed at onset, and 13 had follow-up examinations. Enzyme histochemical and immunohistochemical techniques were applied and BM features evaluated by a semiquantitative scoring system. Clinical findings consisted of pancytopenia associated with a left-shifted differential count of the peripheral blood (less than 5% blasts) and no or minor splenomegaly. During follow-up (median survival 9 months) 35 patients developed severe BM insufficiency and 10 transformed into overt AML. Although myelofibrosis was a characteristic finding, other BM features proved to be heterogeneous. Cellularity was reduced in 13 and increased in 25 specimens. Most prominent was a left-shifted, often macrocytic erythropoiesis and a maturation defect of the neutrophil series. In 15 patients an increase (less than 20%) in CD34+ progenitors, immature myelomonocytic cells, and megakaryoblasts was noted. Abnormalities of megakaryocytes (atypical microforms, clustering, dysplasia) were regularly present. The stroma showed an inflammatory reaction (perivascular plasmacytosis, lymphoid nodules, many macrophages, iron deposits) in about 50% of the samples. Sequential BM biopsies revealed an accumulation of lysozyme-expressing myelomonocytic and CD34+ progenitor cells suggesting an increase in blasts. In conclusion, APMF may not be a distinct entity, but includes hyperfibrotic myelodysplastic syndromes (MDS) either primary or secondary, a rare form of initial AML with fibrosis, and even cases of toxic myelopathy.