Presence Of Bone Marrow Fibrosis Research Articles

Prognostic Impact of Bone Marrow Fibrosis and Effects of Tyrosine Kinase Inhibitors on Bone Marrow Fibrosis in Chronic Myeloid Leukemia

BackgroundMyelofibrosis is reported in around 40% of newly diagnosed chronic myeloid leukemia (CML) patients and have an important role in the pathobiology and prognosis of CML. This retrospective study aimed to evaluate the effects of bone marrow (BM) fibrosis on disease prognosis and the effects of specific tyrosine-kinase inhibitors (TKIs) on BM fibrosis in CML patients. MethodsThe study included 96 patients (>18 years) diagnosed with chronic phase (CP) CML. The clinical and demographic information were collected from the medical files. Post-treatment BM aspirate and core biopsy samples were analyzed for the presence of fibrosis and dysplasia. ResultsThe mean age of the study patients was 52.69 years; 47.9% of the patients were female. At the onset, 53 (63.1%) patients had BM fibrosis. The difference in the overall survival of the patients with respect to BM fibrosis grades was significant (p = .001). Within the BM fibrosis grade groups, there were significant differences between grade 0 vs. grade 2, grade 0 vs. grade 3, and grade 1 vs. grade 3 (p = .005, p = .002, and p = .003 respectively) There was no significant association between the presence of BM fibrosis at the onset and not responding to first-line therapy (p = .724). Moreover, no significant association was found between the presence of BM fibrosis at the onset and molecular (p = .623) or cytogenetic response (p = .535) to first-line therapy. Additionally, the association between the type of second-line and third-line therapy and molecular response (p = .773 and p = .424, respectively) or cytogenetic response (p = .298 and p = .641) was not significant. ConclusionAlthough BM fibrosis seems to be a crucial complication of CML with a poor prognosis, it can be reversed via TKI treatment which may result in improved survival. It might be considered to check the BM for this complication on a regular basis during therapies to test its prognostic influence in CML patients in prospective controlled trials. Further studies focused on this issue are required to utilize BM fibrosis as a candidate prognostic factor.

Can plasma fibrinogen level predict bone marrow fibrosis?

Objective: We aimed to assess the possible relationship between plasma fibrinogen level and bone marrow fibrosis (BMF) grades in
 patients who had undergone bone marrow (BM) biopsy for any reason.
 Patients and Method: This retrospective cohort study included 106 participants aged 18 years and over who had undergone
 simultaneous BM biopsy and circulatory fibrinogen level measurement during 2020 and 2021 at our center. BMF grade was measured
 by the modified Bauermeister grading system (MBGS). Participants were divided into two groups according to MBGS as those without
 BMF and those with BMF.
 Results: Fifty-eight male were included in our study, and the median age of the patients was 63 (range: 19-97) years. Fibrinogen
 (p=0.004) and lactate dehydrogenase (LDH) (p=0.030) levels were significantly higher in the fibrosis group. Multiple regression
 revealed that high fibrinogen (≥359) and high LDH (≥238) were independently associated with a higher likelihood of fibrosis presence
 (adjusted for age and sex); however, diagnostic analyses revealed low accuracy.
 Conclusion: High plasma fibrinogen and LDH levels were found to be independently associated with the presence of BMF. However,
 it was also evident that neither of these parameters could be used for diagnostic purposes.

Anagrelide in essential thrombocythemia: Efficacy and long-term consequences in young patient population

According to the current treatment recommendations, anagrelide, an oral antiplatelet agent, is recommended as a second-line therapy for patients with high-risk essential thrombocythemia experiencing intolerance or refractoriness to first-line approach, such as hydroxyurea or pegylated interferon alpha-2a. If there is a need for introduction of cytoreductive treatment in young patients with a perspective of lifelong exposure, both the efficacy and long-term outcomes should be known. We present the analysis of 48 young patients, diagnosed with essential thrombocythemia below the age of 60, who were exposed to anagrelide treatment for over 10 years. Our observations show that the highest proportion of complete remissions without adverse events and disease progression is seen in the JAK2-mutated patients. By evaluating the changes in hemoglobin concentration and serum erythropoietin throughout the study, we were able to reveal the development of progressive anemia, resulting from diminished susceptibility to erythropoietin and unrelated to bone marrow fibrosis, in patients harboring CALR mutation. Additionally, occurrence of new bone marrow fibrosis was confirmed in seven JAK2-unmutated patients at the end of the study. In summary, in young patient population, we recommend limiting the use of anagrelide to JAK2-mutated subgroup, reducing exposure time and underline the importance of periodic monitoring for the presence of bone marrow fibrosis.

Presence of bone marrow fibrosis in multiple myeloma may predict extramedullary disease.

We analyzed the incidence of bone marrow fibrosis in 91 newly diagnosed Japanese multiple myeloma (MM) patients and evaluated the impact of fibrosis on clinical characteristics and therapeutic outcomes. Thirty-four (37%) patients had greater than grade 1 bone marrow fibrosis. The presence of bone marrow fibrosis did not affect laboratory data, the percentage of plasma cells in bone marrow or cytogenetic findings. It also had no significant effect on response to initial treatment, engraftment after autologous hematopoietic stem cell transplantation or overall survival. Interestingly, the incidence of extramedullary disease at diagnosis was significantly higher in patients with bone marrow fibrosis (p = 0.006). Analysis of biological characteristics of MM cells revealed that expression of CD49e, an alpha5/beta1 integrin, was downregulated in MM cells derived from patients with bone marrow fibrosis (p = 0.026). When seven of the original 34 patients were re-evaluated for fibrosis grading after treatment, five (71%) showed a reduction in fibrosis. Our present findings suggest that the presence of bone marrow fibrosis may predict development of extramedullary disease in MM.

PB2152 THE ROLE OF THE BONE MARROW MICROENVIRONMENT AND CYTOKINES IN THE PROGRESSION OF MONOCLONAL GAMMAPATHY AND MULTIPLE MYELOMA IN PATIENTS OF THE GOMEL REGION OF BELARUS

Background:Multiple myeloma (MM) is an incurable tumor of hematopoietic tissue. In its development, it goes through a stage of monoclonal gammopathy (MGUS) or smoldering myeloma, when a tumor clone is born. With monoclonal gammopathy, the percentage of clonal plasma cells is less than 10%, therefore, during cytological examination of the bone marrow, it is not always possible to determine any specific differences between myeloma cells and normal plasma, therefore, an immunohistochemical study of the bone marrow and a combination of various biochemical markers help in this situation.Aims:Assess the role of the bone marrow microenvironment and the prognostic significance of some cytokines in the progression of diseases in monoclonal gammopathy and multiple myeloma.MethodsThe study was carried out on samples of whole venous blood, aspirate and bone marrow biopsy material of 30 patients (12 patients with monoclonal gammapathy and 18 patients with multiple myeloma). The median age was 64 years for MGUS and 65 years for MM.All patients have undergone blood tests for cytokines, immunoglobulins, kappa and lambda light chains, cytological, immunophenotypic and immunohistochemical studies of the bone marrow. Results were evaluated at the time of diagnosis. The number of clonal plasma cells in the bone marrow in patients with MGUS averaged 3.5% (0.6‐11.2%), in patients with MM 42.2% (12.2‐72.6%). According to immunochemical variants, MM and MGUS are represented by secretion of IgG, IgA, IgM, secretion of kappa and lambda light chains. The level of CD138 positive cells, kappa, lambda chains, the myelokariocyte count, the presence of bone marrow fibrosis were assessed immunohistochemically.Results:When comparing immunohistochemical data for MGUS and MM at the time of diagnosis, a significant excess of the level of CD138 positive cells was found with a significant excess of the count of kappa and lambda light chains in blood serum and bone marrow in patients with MM. In patients with MGUS, the CD138 positive cell count during immunohistochemistry was significantly higher than in the bone marrow immunophenotypic study (p <0.0001) and was accompanied by significant kappa or lambda chains expression in the peripheral blood and bone marrow, which may indicate a possible early generalization of the process and MGUS progression in MM. In all patients with MGUS and expressed expression of CD138 positive cells, the immunohistochemical study showed a significant excess of TNF (p <0.001; r = 0.693), interleukin‐6, interleukin‐8, and were accompanied by lambda light chain secretion (p <0.001; r = 0.698), which suggests the production of cytokines by tumor plasma cells. During follow‐up (6 months) in two MGUS patients with these characteristics, the disease transformed into MM and in one patient with IgM secretion into Waldenstrom macroglobulinemia. Fibrotic changes in the bone marrow during MGUS were combined with lambda light chain production, increased production of interleukin‐6 and interleukin‐8, a decrease in the number of megakaryocytes in the bone marrow (p <0.001; r = 0.698), which may indicate a bone marrow reassociation associated with possible tumor progression.Summary/Conclusion:When analyzing the results of bone marrow immunohistochemical indicators, blood cytokines in our study revealed an increase in the number of CD138 positive cells and a significant excess of cytokines in the producing tumor cells in MGUS, the appearance of fibotic changes and a decrease in the number of myelokariocyte, which can be a significant biomarker of the risk of progression in monoclonal gammapathy.

The presence of bone marrow fibrosis is associated with poorer prognosis in newly diagnosed multiple myeloma treated with immunomodulatory agents and/or proteasome inhibitors.

e19514 Background: The treatment of newly diagnosed multiple myeloma (NDMM) has evolved significantly with the advent of the immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs). While the presence of bone marrow fibrosis (BMF) has previously been associated with poor prognosis in multiple myeloma (MM), these studies were small and conducted prior to the widespread use of IMiDs and PIs. Here, we determined the incidence of BMF in NDMM patients and correlated the degree of BMF with prognosis in a population enriched for IMiD and/or PI exposure. Methods: Bone marrow biopsies from 306 MM patients seen at Duke between 2003 and 2013 were screened for BMF using a reticulin stain. Samples were scored as absent, mild, moderate, or severe fibrosis based on the degree and intensity of staining. The association between presence and degree of BMF to progression free survival (PFS) and overall survival (OS) was calculated using Kaplan-Meier analysis. Results: Of the 306 patients evaluated, 248 (81.0%) were treated with an IMiD, 241 (78.8%) were treated with a PI, and 217 (70.9%) received both. Additionally, 160 (52.3%) patients went on to receive an autologous stem cell transplant (HSCT). A total of 193 patients (63.1%) were evaluable for BMF. Of these, 96 (49.7%) had detectable BMF, while 97 (50.3%) had no BMF. The degree of BMF was mild in 60 patients (62.5%), and moderate or severe in 34 patients (35.4%). Median PFS in patients without BMF was 30.4 months, and 21.8 months in patients with BMF present (log-rank p = 0.02). Median OS was 61.1 months in patients without BMF, and 46.3 months in patients with BMF (log-rank p = 0.048). Patients with moderate or severe BMF had a particularly poor prognosis with a PFS of only 18.8 months and an OS of 32.7 months. Conclusions: Our study represents the largest dataset to date examining the incidence of BMF in MM patients, and is the only one to examine the association of BMF with prognosis in the era of novel therapies and widespread use of HSCT. Our data suggests that BMF is common in NDMM, and MM patients with BMF (particularly those with more extensive BMF) have a poorer prognosis even when treated with IMiDs and PIs. These data emphasize the importance of determining the presence and degree of BMF at time of MM diagnosis, and suggest a role for adjunctive therapies that target BMF in MM patients with co-existing BMF.

Bone marrow fibrosis in chronic myelomonocytic leukemia is associated with increased megakaryopoiesis, splenomegaly and with a shorter median time to disease progression.

Bone marrow (BM) fibrosis is an adverse prognostic marker in several myeloid neoplasms, particularly in myelodysplastic syndrome (MDS) with fibrosis; however, its significance in chronic myelomonoctyic leukemia (CMML) has not been evaluated. We performed a retrospective analysis to investigate the prognostic and clinicopathological features of CMML with and without BM fibrosis. The study included specimens from a total of 83 untreated CMML patients from 2 large institutions. Patients with any amount of BM fibrosis (MF-1 or higher; MF1+) had significantly shorter progression-free survival (MF1+, 28.3 months vs MF0, not reached; p = 0.001, log rank test), splenomegaly (p = 0.016), and increased BM megakaryocytes (p = 0.04) compared to patients without BM fibrosis (MF-0). No association was observed between fibrosis and peripheral blood parameters, presence of JAK2 V617F mutation, BM blasts, or overall survival. Our study demonstrates the importance of assessing BM fibrosis in CMML. Similar to MDS, the presence of BM fibrosis may identify a distinct subgroup of CMML patients (CMML-F) with a more aggressive clinical course.

Imatinib reduces bone marrow fibrosis and overwhelms the adverse prognostic impact of reticulin formation in patients with chronic myeloid leukaemia

AimsBefore the era of tyrosine kinase inhibitors (TKIs), the presence of bone marrow fibrosis (MF) in patients with chronic myeloid leukaemia (CML) has been established as a poor prognostic factor....

Bone Marrow Fibrosis In Patients With Multiple Myeloma: A New Prognostic Factor For Survival?

IntroductionMultiple myeloma (MM) is characterized by the proliferation of plasma cells in the bone marrow and a secretion of monoclonal immunoglobulins. Survival in MM is very variable and multiple factors are known to influence prognosis such as age, ISS stage, and genetic abnormalities. Fibrosis can be found in the bone marrow of MM patients but the literature reporting the incidence of fibrosis and its effect on prognosis is very limited.The purpose of this study was to estimate the incidence of bone marrow fibrosis in MM patients and its effect on survival. Materials and methodsData was collected at the Karolinska University Hospital in Solna, Sweden and information obtained from the hospital's records. We gathered information on all patients diagnosed with MM between 2003 and 2011. All bone marrow reports were reviewed and the presence of bone marrow fibrosis (evaluated using reticulin staining) at diagnosis was recorded. Fibrosis was graded as 1 (mild), 2 (significant) and 3 (advanced), in accordance with WHO 2008 criteria. Patients with fibrosis were paired with patients without fibrosis (matched by sex, birth year, and year of diagnosis). Survival comparing MM patients with and without fibrosis was evaluated using Kaplan-Meier estimate and Cox regression model. ResultsA total of 586 individuals, 327 males and 259 females, were diagnosed with MM at the Karolinska University Hospital, Solna during 2003 – 2011. Evidence of bone marrow fibrosis was noted in 223 (38%) patients at diagnosis, and 175 had fibrosis grade 1, 33 grade 2, and 15 grade 3. No significant difference was observed between males (N = 135) and females (N = 88) (p = 0.085). Mean age at diagnosis was significantly lower for patients with fibrosis (67.1 years) than in patients without fibrosis (69.7 years) (p = 0.013).Compared with paired patients without fibrosis (N = 217), patients with fibrosis had significantly worse survival (Figure), being 5.0 years vs. 4.4 years, respectively (relative risk (RR)=1.3, 95% confidence interval (CI) 1.00-1.70; p= 0.049). The difference was greatest in male patients and patients younger than 65 years at diagnosis. Survival was worse in patients with advanced fibrosis, 4.5 (95% CI 3.6-6.4) years for grade 1 fibrosis, and 3.0 (95% CI 1.6-NA) years for higher degree of fibrosis. [Display omitted] ConclusionIn this study, based on almost 600 patients with MM we show that bone marrow fibrosis is common at diagnosis (38%). Importantly, our findings show that the presence of fibrosis was associated with inferior survival. More studies are needed regarding the underlying causes for these findings, including treatment response, treatment-related complications and relation to other known prognostic factors. Disclosures:No relevant conflicts of interest to declare.

Outcome of Acute Myeloid Leukemia AML &High Risk MDS Treated According to the Standard of Care in Community Hospital, Data From Single Center ( 2001–2010)

Abstract 4796 Background:Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults causing the highest number of annual deaths secondary to leukemias in the United States. Age, cytogenetics, molecular features are the most important factors in the prognosis, whereby increased age and monosomal karyotypes carry the worst prognosis. The most favorable cytogenetics are patients with normal karyotypes, who can receive standard therapy. Aim:Study the overall survival (OS) of AML/High risk MDS treated according to standard of care at a community teaching hospital. Methods:A retrospective study of AML & High risk MDS patients treated at AGMC, Akron, Ohio USA, during 2002–2010. After IRB approval, we reviewed patient demographics, diagnosis types/subtypes, treatment, and cytogenetics. Patients were classified as low-intermediate risk or high risk according to cytogenetics background using WHO criteria. We also classified patients according to presence of bone marrow fibrosis and health insurance coverage at the time of diagnosis. Overall survival (OS) rates were determined by Kaplan-Meier Survival Analysis. Prognostic factors were evaluated by Log Rank analysis. Results:We were able to classify 98 (75%) pts, with 52 (53%) pts as high risk and 46 (47%) pts as low-intermediate risk. Median age was 55 years (range: 19–90), 43 (45%) pts were older than 75 years. AML pts made up 71%, 45 patients (35%) had complex cytogenetics, and 15% had AML arise from MDS. Median survival overall was 22.4 weeks; 14.4 weeks for high risk and 53.8 weeks for low risk (p<0.01). Median survival for pts greater than 75 years was 11.5 weeks compared to 35.8 weeks for those younger than 75 years (p<0.05). We classified 103 pts according to insurance; 29 pts had private insurance and 74 pts had medicare/Medicaid. Cox regression analysis was performed to examine for the net effect of each of age, insurance, and fibrosis status after controlling for the effect of other variables in the model. Data showed that survival is inversely related to age at diagnosis (p value=.01) while the variables fibrosis status, medicaid/uninsured, and private insurance did not contribute significantly to the model (p value=.97 and.14.34, respectively). Conclusions:No significant differences in OS regarding insurance status or presence of bone marrow fibrosis. This was likely because the majority of pts received standard of care therapy and overall survival, in general, was low in the study population. OS was lowest in high risk patients and those greater than 75 years, and was better in low risk pts and those younger than 75 years respectively. Early referral to a specialized center, or possible clinical trial enrollment may be an alternative way to approach those pts. Disclosures:No relevant conflicts of interest to declare.

Acquired Delta-Storage Pool Deficiency Associated with Idiopathic Myelofibrosis

A 73-year-old woman complained of easy bruising, as a consequence of prolonged bleeding time despite normal platelet counts. Platelet aggregation profile, mepacrine fluorescence test, flow cytometry and transmission electron microscopy studies led to the diagnosis of delta-storage pool deficiency (SPD) A few months later, she developed hyperleucocytosis with immature granulocytes and erythroblasts. The presence of bone marrow fibrosis and clonal cytogenetic abnormalities led to the diagnosis of idiopathic myelofibrosis (IM). Association between SPD and IM has never been reported. The pathogenesis of this unusual association remains unclear and may involve proliferation of abnormal monoclonal stem cells with differentiation into activated megakaryocytes associated with impaired dense granule development and increased cytokines release which may be. involved in myelofibrosis.

Down's Syndrome and Acute Leukemia in Children: An Analysis of Phenotype by Use of Monoclonal Antibodies and Electron Microscopic Platelet Peroxidase Reaction

The clinical, hematologic, and immunophenotypic features in 20 patients with Down's syndrome (DS) and acute leukemia were analyzed. Of the 20 patients, all 14 patients who were 3 years old and less were diagnosed as having acute megakaryoblastic leukemia (AMKL) by use of platelet-specific monoclonal antibodies and platelet peroxidase (PPO) reaction in electron microscopy. They were characterized by the presence of bone marrow fibrosis, having a history of myelodysplastic syndrome (MDS) and a poor response to chemotherapy. Only one patient has remained in continuous complete remission for more than 1 year. Acute leukemia in six patients who were older than 4 years was classified as common acute lymphoblastic leukemia antigen (CALLA)-positive acute lymphoblastic leukemia (ALL). In one of six patients classified as ALL, the leukemic blasts simultaneously expressed myeloid-associated surface antigens. All six patients achieved a complete remission and have remained in continuous complete remission and have remained in continuous complete remission from 10 to 52 months from the initial diagnosis. Although it has been suggested that the distribution of types of acute leukemia in patients with DS is similar to that in normal children, the present study shows that the distribution of acute leukemia types is quite different from that in patients without Down's syndrome.

Down's syndrome and acute leukemia in children: an analysis of phenotype by use of monoclonal antibodies and electron microscopic platelet peroxidase reaction [see comments

The clinical, hematologic, and immunophenotypic features in 20 patients with Down's syndrome (DS) and acute leukemia were analyzed. Of the 20 patients, all 14 patients who were 3 years old and less were diagnosed as having acute megakaryoblastic leukemia (AMKL) by use of platelet- specific monoclonal antibodies and platelet peroxidase (PPO) reaction in electron microscopy. They were characterized by the presence of bone marrow fibrosis, having a history of myelodysplastic syndrome (MDS) and a poor response to chemotherapy. Only one patient has remained in continuous complete remission for more than 1 year. Acute leukemia in six patients who were older than 4 years was classified as common acute lymphoblastic leukemia antigen (CALLA)-positive acute lymphoblastic leukemia (ALL). In one of six patients classified as ALL, the leukemic blasts simultaneously expressed myeloid-associated surface antigens. All six patients achieved a complete remission and have remained in continuous complete remission and have remained in continuous complete remission from 10 to 52 months from the initial diagnosis. Although it has been suggested that the distribution of types of acute leukemia in patients with DS is similar to that in normal children, the present study shows that the distribution of acute leukemia types is quite different from that in patients without Down's syndrome.

Increased Circulating CSF-1 (M-CSF) in Myeloproliferative Disease: Association With Myeloid Metaplasia and Peripheral Bone Marrow Extension

Myeloproliferative disease (MPD) is heterogeneous in phenotypic expression and may display features consistent with expansion and activation of the monocyte/macrophage population during its course. The role of colony-stimulating factor-1 (CSF-1) in the pathophysiology of MPD was investigated by measuring circulating CSF-1 levels and examining their relationship to disease phenotype. Serum CSF-1 concentrations, measured by radioimmunoassay, were elevated in all MPD phenotypes. CSF-1 levels differed significantly between groups of patients with essential thrombocythemia, polycythemia vera, and postpolycythemic or agnogenic myeloid metaplasia (in ascending order). CSF-1 serum levels were positively correlated with spleen size and the degree of peripheral bone marrow extension, determined by scintigraphy using a macrophage-seeking isotope. There was no correlation between CSF-1 concentration and circulating levels of erythrocytes, neutrophils or platelets, or the presence of bone marrow fibrosis. Elevated serum CSF-1 levels appear to be associated with an expanded monocyte/macrophage population in MPD. In view of the known cooperativity between CSF-1 and other growth factors in regulating hematopoiesis, the finding of increased serum CSF-1 concentrations and its association with myeloid metaplasia and bone marrow extension may indicate a pathophysiologic role for CSF-1 in determining the phenotypic expression of MPD.

Increased circulating CSF-1 (M-CSF) in myeloproliferative disease: association with myeloid metaplasia and peripheral bone marrow extension

Myeloproliferative disease (MPD) is heterogeneous in phenotypic expression and may display features consistent with expansion and activation of the monocyte/macrophage population during its course. The role of colony-stimulating factor-1 (CSF-1) in the pathophysiology of MPD was investigated by measuring circulating CSF-1 levels and examining their relationship to disease phenotype. Serum CSF-1 concentrations, measured by radioimmunoassay, were elevated in all MPD phenotypes. CSF-1 levels differed significantly between groups of patients with essential thrombocythemia, polycythemia vera, and postpolycythemic or agnogenic myeloid metaplasia (in ascending order). CSF-1 serum levels were positively correlated with spleen size and the degree of peripheral bone marrow extension, determined by scintigraphy using a macrophage-seeking isotope. There was no correlation between CSF-1 concentration and circulating levels of erythrocytes, neutrophils or platelets, or the presence of bone marrow fibrosis. Elevated serum CSF-1 levels appear to be associated with an expanded monocyte/macrophage population in MPD. In view of the known cooperativity between CSF-1 and other growth factors in regulating hematopoiesis, the finding of increased serum CSF-1 concentrations and its association with myeloid metaplasia and bone marrow extension may indicate a pathophysiologic role for CSF-1 in determining the phenotypic expression of MPD.

Leukemias with megakaryoblastic involvement: clinical, hematologic, and immunologic characteristics

The clinical, hematologic, and phenotypic features of 28 patients with acute leukemia with megakaryocytic involvement (AMKL) were analyzed. The prevalence of this type of leukemia in the entire series was 11.6%, with a higher incidence among patients with acute transformation of a previous myeloproliferative disorder (MPD) (24%) than among the transformed myelodysplastic syndrome (13%) patients. The incidence in the “de novo” ANLL was 8% and 16% among secondary leukemias. The presence of bone marrow fibrosis together with low WBC and normal or increased platelet counts despite a severe anemia are the most relevant features in these patients who otherwise displayed an apparently poor prognosis. Megakaryoblasts were morphologically recognized more frequently in the acute transformations of MPD than in de novo ANLL. Only two cases were considered pure AMKL, and in the remaining 26 patients, megakaryoblasts coexisted with other granulomonocytic and/or erythroid populations. Antiglycoprotein IIIa (anti-GPIIIa) (C17) and anti-GPIIb/IIIa (CDw41-, J15-) antibodies are probably the best markers for AMKL, although the monoclonal antibody against GPIX (FMC25) was also positive in a majority of cases but in a lower percentage of cells. On the other hand, megakaryoblasts were generally negative for granulocytic or monocytic markers (CD13, CD14, CD15); the expression of HLA-DR antigens in these cells was variable. Our present results indicate that megakaryoblastic involvement is more common than previously recognized. This is true not only in acute transformed leukemias but also in de novo ANLL. Although the diagnosis of these cases should be based on megakaryocytic markers, it is often possible to suspect a diagnosis according to certain clinical and hematologic features.

Leukemias With Megakaryoblastic Involvement: Clinical, Hematologic, and Immunologic Characteristics

The clinical, hematologic, and phenotypic features of 28 patients with acute leukemia with megakaryocytic involvement (AMKL) were analyzed. The prevalence of this type of leukemia in the entire series was 11.6%, with a higher incidence among patients with acute transformation of a previous myeloproliferative disorder (MPD) (24%) than among the transformed myelodysplastic syndrome (13%) patients. The incidence in the "de novo" ANLL was 8% and 16% among secondary leukemias. The presence of bone marrow fibrosis together with low WBC and normal or increased platelet counts despite a severe anemia are the most relevant features in these patients who otherwise displayed an apparently poor prognosis. Megakaryoblasts were morphologically recognized more frequently in the acute transformations of MPD than in de novo ANLL. Only two cases were considered pure AMKL, and in the remaining 26 patients, megakaryoblasts coexisted with other granulomonocytic and/or erythroid populations. Antiglycoprotein IIIa (anti-GPIIIa) (C17) and anti-GPIIb/IIIa (CDw41-, J15-) antibodies are probably the best markers for AMKL, although the monoclonal antibody against GPIX (FMC25) was also positive in a majority of cases but in a lower percentage of cells. On the other hand, megakaryoblasts were generally negative for granulocytic or monocytic markers (CD13, CD14, CD15); the expression of HLA-DR antigens in these cells was variable. Our present results indicate that megakaryoblastic involvement is more common than previously recognized. This is true not only in acute transformed leukemias but also in de novo ANLL. Although the diagnosis of these cases should be based on megakaryocytic markers, it is often possible to suspect a diagnosis according to certain clinical and hematologic features.