A phase I study of pevonedistat, azacitidine, and venetoclax in patients with relapsed/refractory acute myeloid leukemia.

Azacitidine/venetoclax is an active regimen in patients with newly diagnosed acute myeloid leukemia (AML). However, primary or secondary resistance to azacitidine/venetoclax is an area of unmet need and overexpression of MCL1 is suggested to be a potential resistance mechanism. Pevonedistat inhibits MCL1 through activation of NOXA, and pevonedistat/azacitidine has previously shown activity in AML. To assess the tolerability and efficacy of adding pevonedistat to azacitidine/ venetoclax in relapsed/refractory AML, we conducted a phase I, multicenter, open-label study in 16 adults with relapsed/ refractory AML. Patients were treated with azacitidine, venetoclax along with pevonedistat intravenously on days 1, 3 and 5 of each 28-day cycle at doses of 10, 15 or 20 mg/m2 in successive cohorts in the dose escalation phase. The impact of treatment on protein neddylation as well as expression of pro-apoptotic BCL2 family members was assessed. The recommended phase II dose of pevonedistat was 20 mg/m2. Grade 3 or higher adverse events included neutropenia (31%), thrombocytopenia (13%), febrile neutropenia (19%), anemia (19%), hypertension (19%) and sepsis (19%). The overall response rate was 46.7% for the whole cohort including complete remission in five of seven (71.4%) patients who had not previously been treated with the hypomethylating agent/venetoclax. No measurable residual disease was detected in 80.0% of the patients who achieved complete remission. The median time to best response was 50 (range, 23-77) days. Four patients were bridged to allogeneic stem cell transplantation. The combination of azacitidine, venetoclax and pevonedistat is safe and shows encouraging preliminary activity in patients with relapsed/refractory AML. (NCT04172844).

Primary Bone Lymphoma Masquerading as Multiple Myeloma: Challenges in the Diagnostic Workup of Severe Hypercalcemia.

In this case, we explore the diagnostic workup of a patient presenting with symptomatic hypercalcemia. Initially suspected to have multiple myeloma, the diagnostic evaluation instead unveiled non-germinal center (non-GC) diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common histologic subtype of non-Hodgkin lymphoma and is heterogeneous in terms of presentation, genetic drivers, and morphology. As primary bone DLBCL is exceedingly rare, the case presented proved to be a diagnostic challenge. The patient presented with one week of weakness, one to two days of nausea, and leg pain. On admission, hypercalcemia, renal failure, anemia, and lytic bone lesions were present and suggestive of multiple myeloma. However, serum protein electrophoresis and immunoglobulin levels did not fit the 2016 World Health Organization (WHO) diagnostic criteria for multiple myeloma. A negative bone marrow biopsy also argued against a diffuse plasma cell neoplasm. Finally, a biopsy from another bone lesion was diagnostic of DLBCL. This case discusses an unusual presentation of DLBCL.

Discordant pathologic diagnoses of myelodysplastic neoplasms and their implications for registries and therapies.

Myelodysplastic neoplasms (MDS) are a collection of hematopoietic disorders with widely variable prognoses and treatment options. Accurate pathologic diagnoses present challenges because of interobserver variability in interpreting morphology and quantifying dysplasia. We compared local clinical site diagnoses with central, adjudicated review from 918 participants enrolled in the ongoing National Heart, Lung, and Blood Institute National MDS Natural History Study, a prospective observational cohort study of participants with suspected MDS or MDS/myeloproliferative neoplasms (MPNs). Locally, 264 (29%) were diagnosed as having MDS, 15 (2%) MDS/MPN overlap, 62 (7%) idiopathic cytopenia of undetermined significance (ICUS), 0 (0%) acute myeloid leukemia (AML) with <30% blasts, and 577 (63%) as other. Approximately one-third of cases were reclassified after central review, with 266 (29%) diagnosed as MDS, 45 (5%) MDS/MPN overlap, 49 (5%) ICUS, 15 (2%) AML with <30%, and 543 (59%) as other. Site miscoding errors accounted for more than half (53%) of the local misdiagnoses, leaving a true misdiagnosis rate of 15% overall, 21% for MDS. Therapies were reported in 37% of patients, including 43% of patients with MDS, 49% of patients with MDS/MPN, and 86% of patients with AML with <30% blasts. Treatment rates were lower (25%) in cases with true discordance in diagnosis compared with those for whom local and central diagnoses agreed (40%), and receipt of inappropriate therapy occurred in 7% of misdiagnosed cases. Discordant diagnoses were frequent, which has implications for the accuracy of study-related and national registries and can lead to inappropriate therapy. This trial was registered at www.clinicaltrials.gov as #NCT05074550.

Utility of targeted gene sequencing to differentiate myeloid malignancies from other cytopenic conditions.

The National Heart, Lung, and Blood Institute-funded National MDS Natural History Study (NCT02775383) is a prospective cohort study enrolling patients with cytopenia with suspected myelodysplastic syndromes (MDS) to evaluate factors associated with disease. Here, we sequenced 53 genes in bone marrow samples harvested from 1298 patients diagnosed with myeloid malignancy, including MDS and non-MDS myeloid malignancy or alternative marrow conditions with cytopenia based on concordance between independent histopathologic reviews (local, centralized, and tertiary to adjudicate disagreements when needed). We developed a novel 2-stage diagnostic classifier based on mutational profiles in 18 of 53 sequenced genes that were sufficient to best predict a diagnosis of myeloid malignancy and among those with a predicted myeloid malignancy, predict whether they had MDS. The classifier achieved a positive predictive value (PPV) of 0.84 and negative predictive value (NPV) of 0.8 with an area under the receiver operating characteristic curve (AUROC) of 0.85 when classifying patients as having myeloid vs no myeloid malignancy based on variant allele frequencies (VAFs) in 17 genes and a PPV of 0.71 and NPV of 0.64 with an AUROC of 0.73 when classifying patients as having MDS vs non-MDS malignancy based on VAFs in 10 genes. We next assessed how this approach could complement histopathology to improve diagnostic accuracy. For 99 of 139 (71%) patients (PPV of 0.83 and NPV of 0.65) with local and centralized histopathologic disagreement in myeloid vs no myeloid malignancy, the classifier-predicted diagnosis agreed with the tertiary pathology review (considered the internal gold standard).

How I Diagnose Mature T-Cell Proliferations by Flow Cytometry.

OBJECTIVES: Mature T-cell neoplasms are a challenging area of diagnostic hematopathology. Flow cytometry has emerged as a useful technique for T-cell assessment. METHODS: We discuss the application of flow cytometry to the evaluation of mature T-cell proliferations, to include illustrative cases, theoretical framework, detailed review of normal and reactive T-cell subsets, and examination of diagnostic pitfalls. RESULTS: Immunophenotypic aberrancy can be construed as a direct expression of the neoplastic phenotype, in contrast to clonal expansion, which is seen in reactive and neoplastic T-cell proliferations. Major and minor T-cell subsets show characteristic patterns of antigen expression. Reactive states can manifest expansions of normal minor subsets and also show alterations of antigen expression on certain populations. However, some patterns of antigen expression are either never or very rarely encountered in reactive T cells. Flow cytometric tools are now available to directly assess clonality in specific T-cell populations. Technical and biological pitfalls may complicate the interpretation of T-cell flow cytometry. CONCLUSIONS: Flow cytometry is a very useful tool in the diagnostic armamentarium for the assessment of mature T-cell proliferations, but it must be interpreted based on a thorough knowledge of the T-cell immune response, as well as an awareness of clinical context.

Prognostic impact of immunophenotypic aberrancies of blasts in lower risk myelodysplastic syndrome.

OBJECTIVE/BACKGROUND: Low risk myelodysplastic syndrome (MDS) is a marrow failure state eventually leading to transfusion dependence. Flow cytometry has previously been demonstrated as prognostic tool in MDS, however not thoroughly studied in lower risk MDS. In this study, we assessed whether assessment for immunophenotypic blast aberrancies by flow in low risk MDS patients has a prognostic role in these patients. METHODS: A total of 63 consecutive patients diagnosed with low/intermediate risk MDS were included. We recorded initial flow results, and collected time to transfusion dependence, and AML progression. RESULTS: On multivariate cox regression analysis, increasing IPSS-R score, an increase in the number of blast aberrancies on flow cytometry, and aberrant expression of CD7 on myeloid blasts increased likelihood of transfusion dependence. CONCLUSION: Low risk MDS patients with increasingly aberrant blast phenotypes by flow may be at risk for earlier transfusion dependence.

Assessment of Molecular Residual Disease Using Circulating Tumor DNA to Identify Multiple Myeloma Patients at High Risk of Relapse.

BACKGROUND: Despite treatment with high-dose chemotherapy followed by autologous stem cell transplantation (AHCT), patients with multiple myeloma (MM) invariably relapse. Molecular residual disease (MRD)-negativity post-AHCT has emerged as an important prognostic marker predicting the duration of remission. Current techniques for MRD assessment involve bone marrow (BM) aspirate sampling, which is invasive, subject to sample variability and is limited by spatial heterogeneity. We compared the performance of a non-invasive, circulating tumor DNA (ctDNA)-based MRD assay with multiparameter flow cytometry (MFC) of marrow aspirate to predict relapse in AHCT recipients with MM. METHODS: MRD assessment using ctDNA was retrospectively analyzed on 80 plasma samples collected at different time points from 28 patients, post-AHCT. MFC was used to assess MRD from BM biopsy. Individual archived BM aspirate slides or formalin-fixed paraffin-embedded slides from the time of MM diagnosis and matched blood were used to assess MRD at 3 months, post-AHCT, using a personalized, tumor-informed ctDNA assay. RESULTS: ctDNA was detectable in 70.8% (17/24) of pre-AHCT patients and 53.6% (15/28) of post-AHCT patients (3-month time point). Of the 15 post-AHCT ctDNA-positive patients, 14 relapsed on follow-up. The median PFS for ctDNA-positive patients was 31 months, and that for ctDNA-negative patients was 84 months (HR: 5.6; 95%CI: 1.8-17;p=0.0003). No significant difference in PFS was observed in patients stratified by MFC-based MRD status (HR 1.2; 95%CI: 0.3-3.4;p=0.73). The positive predictive value for ctDNA was also significantly higher than MFC (93.3% vs. 68.4%). CONCLUSIONS: This study demonstrates tumor-informed ctDNA analysis is strongly predictive of MM relapse.

Post-transplant primary cutaneous peripheral T-cell lymphoma not otherwise specified in a pediatric patient.

Solid organ and hematopoietic stem cell transplantation may be complicated by the development of post-transplant lymphoproliferative disorders (PTLDs). The World Health Organization categorizes PTLDs into four entities including non-destructive, monomorphic, polymorphic, and classical Hodgkin lymphoma types. The most common PTLDs are B-cell lymphomas, with T-cell lymphomas accounting for only a few cases. Cutaneous T-cell lymphomas are rarer still in post-transplant patients with primary cutaneous peripheral T-cell lymphoma being an extraordinarily rare subtype in this population. PTLDs may be aggressive and are often associated with high morbidity and mortality. Advances in medicine have led to increased awareness of PTLDs and improved diagnostic tools which assist in the diagnosis of these conditions. However, the clinical and histopathologic heterogeneity of PTLDs may make diagnosis a challenge. In the transplant patient population, the cutaneous manifestations of the lymphoproliferative disease may mimic other conditions, such as eczematous dermatitis and graft-vs-host disease. Herein, we report a case of post-transplant primary cutaneous peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) in a pediatric heart transplant patient and describe the clinical presentation and diagnostic histopathologic features.

Comparison of salvage chemotherapy regimens and prognostic significance of minimal residual disease in relapsed/refractory acute myeloid leukemia.

We compared the outcomes of salvage chemotherapy in 146 patients with relapsed (57.5%) or refractory (42.5%) AML who received CLAG-M (51%), MEC (39%) or CLAG (10%). Minimal residual disease (MRD) was assessed by flow cytometry. Bivariate, Kaplan-Meier, and Cox regression analyses were conducted. Complete remission (CR) rate of 46% (CLAG-M 54% versus MEC/CLAG 40%, p = .045) was observed with MRD-negative CR of 33% (CLAG-M 39% versus MEC/CLAG 22%, p = .042). Median overall survival (OS) was 9.7 months; the longest OS occurred with CLAG-M (13.3, 95%CI 2.4-24.3) versus MEC (6.9, 95%CI 2.9-10.9) or CLAG (6.2, 95%CI 2.4-12.6) (p = .025). When adjusted for age, gender, relapsed/refractory AML, poor risk AML, MRD, chemotherapy and transplant, CLAG-M (HR 0.63, 95% CI 0.40-0.98, p = .042), MRD-negativity (HR 0.15, 95% CI 0.07-0.30, p < .001) and transplant (HR 0.22, 95% CI 0.13-0.39, p < .001) were associated with higher OS. Our findings confirm that CLAG-M is a reasonable salvage regimen for RR-AML followed by transplant.

Relapse after Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma: Survival Outcomes and Factors Influencing Them.

Many patients with multiple myeloma (MM) eventually relapse even after allogeneic hematopoietic cell transplantation (alloHCT) for curative intent. Over the past decade, outcomes for patients with MM have improved significantly with the availability of new therapies, including next-generation proteasome inhibitors, immunomodulatory agents, and, more recently, monoclonal antibodies. Although several published studies have evaluated the outcomes of alloHCT for MM, the data on survival outcomes in patients with MM experiencing disease relapse following alloHCT are limited. In addition, the predictors for postrelapse survival in these patients are not known. In this study, we examined the outcomes of a single-center cohort of 60 patients with MM who experienced relapse or progression after alloHCT. In addition, we evaluated the use of salvage regimens for treatment of relapsed MM and analyzed the predictors for improved postrelapse survival. After a median follow-up of 2.2 years from the time of relapse, the median duration of postrelapse survival was 1.8 years (95% confidence interval [CI], 1.2 to 5.0 years). Patients received a median of 3 lines of therapy (range, 0 to 10) for treatment of MM beyond the post-alloHCT relapse/progression. Multivariate analysis identified cytogenetic risk (standard risk versus high risk; hazard ratio [HR], .34; P = .01), time to relapse after alloHCT (>12 months versus ≤12 months: HR, .41; P = .04), and occurrence of acute graft-versus-host disease (GVHD) before relapse (GVHD versus no GVHD: HR, 2.89; P = .01) significantly affected postrelapse survival. These data illustrate that long-term myeloma control and survival is attainable in those relapsing/progressing after alloHCT and suggest that the synergism between novel therapies and the allogeneic immune platform is the key to improved survival in this high-risk patient population.

Simple Laboratory Test Utilization Interventions to Reduce Inappropriate Specialty Coagulation Testing.

OBJECTIVES: The naming convention in coagulation may cause confusion in electronic ordering systems, leading to inappropriate test orders. We implemented test utilization efforts and studied utilization before and after interventions for two specialty coagulation assays. METHODS: Two interventions were implemented: test names were changed from factor assay to activity, and residents reviewed all factor V and X requests. A retrospective review of factor V and X activity orders was performed for the period 1 year before and after interventions. RESULTS: After interventions, factor V and X activity orders decreased by approximately 40%. Resulted tests decreased by 53.8% and 47.8%, corresponding to reductions of $2,493.05 and $1,867.80 per year in laboratory charges for factor V and factor X activity, respectively. Abnormal factor V activity results increased from 45% to 59%. Factor V activity orders from outpatient clinics decreased by 21.6%. CONCLUSIONS: Simple interventions can reduce inappropriate specialty coagulation test orders and unnecessary costs.

Ancillary Studies in the Diagnostic Evaluation of Large B-Cell Lymphoma.

CONTEXT.­: Large B-cell lymphoma classification has changed significantly over the decades, evolving from a purely morphologic categorization to one using sophisticated ancillary studies including molecular analysis, immunohistochemistry, and cytogenetics, in addition to morphology and clinical presentation. OBJECTIVE.­: To discuss and interpret the key ancillary studies required for subclassification in 2019 and review the differential diagnosis of diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). DATA SOURCES.­: Recent literature on the subcategories of large B-cell lymphoma is reviewed, along with relevant updates from the 2016 World Health Organization Classification of Tumours of Hematopoietic and Lymphoid Tissues, with an emphasis on Epstein-Barr virus-positive lymphoproliferative disorders, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and large B-cell lymphoma with IRF4 rearrangement. CONCLUSIONS.­: Cases with DLBCL, NOS histology can be further subclassified on the basis of cell of origin studies, Epstein-Barr virus-encoded small RNAs, MYC and BCL2 and/or BCL6 rearrangement studies, and other relevant cytogenetic and immunohistochemical studies. The diagnosis of DLBCL, NOS is therefore a diagnosis of exclusion.

Carcinocythemia: A rare entity becoming more common? A 3-year, single institution series of seven cases and literature review.

INTRODUCTION: Carcinocythemia is a rare phenomenon defined as morphologically identifiable, circulating tumor cells in the peripheral blood. No modern case series of carcinocythemia exists in the literature. METHODS: Blood smears from carcinocythemia patients were reviewed and associated clinicopathologic findings described and compared to the literature. When available, bone marrows were examined. RESULTS: We identified 7 carcinocythemia cases over 3 years at our institution in 5 females and 2 males with a median age of 57 and compare them to 26 case reports in the literature (19 females, 10 males; median age 57). The primary neoplasms were carcinomas of breast (3 cases), lung, non-small cell (2 cases), prostate (1), and 1 case of unknown primary. Circulating tumor cells were associated with fragmentation hemolysis (2 cases), asplenic RBC changes (3 cases), and myeloid antigen expression by flow cytometry (2 cases) and were most commonly found at the feathered edge of the slide (6 cases) as single cells or in clusters. CONCLUSIONS: This represents the largest series of carcinocythemia reported. The identification of 7 cases at one institution over a 3-year period suggests carcinocythemia may becoming more common. Raising awareness of this entity and its associated clinicopathologic findings may help avoid diagnostic pitfalls in blood smear examinations and may guide timely clinical management.

CD30 Expression in Monomorphic Posttransplant Lymphoproliferative Disorder, Diffuse Large B-Cell Lymphoma Correlates With Greater Regulatory T-Cell Infiltration.

OBJECTIVES: CD30 is a protein thought to promote cell proliferation/survival and downregulate the immune response. Twenty percent to 40% of de novo diffuse large B-cell lymphomas (DLBCLs) express CD30, and some patients have been treated with the anti-CD30 agent brentuximab. In the solid organ transplant setting, allograft regulatory T cells (Tregs) have been shown to be modulated via CD30 signaling. METHODS: Posttransplant lymphoproliferative disorders (PTLDs) constitute a heterogeneous group of lymphomas, and since CD30 expression has been rarely formally assessed in PTLDs, we analyzed a cohort of PTLDs. RESULTS: We found that 26 (79%) of 33 PTLDs were CD30+. Of these, 17 (77%) of 22 DLBCL monomorphic PTLDs were CD30+ compared with 56 (38%) of 148 de novo DLBCLs (P = .009). The median FoxP3+ Treg count was higher in CD30+ than in CD30- PTLDs, 3.0 vs 0 (P = .012). CONCLUSIONS: These findings suggest a pathophysiologic link between CD30 activity and Tregs and may indicate differential expression of CD30 in B-cell lymphomas arising in the setting of immune dysregulation.

Flow Cytometry of B-Cell Neoplasms.

Flow cytometric evaluation is considered a standard ancillary study for the diagnosis of most B-cell lymphoproliferative disorders. Establishing a neoplastic B-cell population depends on identification of light chain restriction or lack of light chain expression in mature neoplasms and demonstration of aberrant antigen expression in both immature and mature neoplasms, as compared with normal counterparts. The immunophenotypes of the most common B-cell neoplasms are herein described, with an emphasis on their immunophenotypic differential diagnosis and prognostic and therapeutic implications.

Evaluation of CD43 expression in non-hematopoietic malignancies.

OBJECTIVES: CD43 is normally expressed only on the surface of leukocytes, and is considered a sensitive and specific marker for hematologic malignancies. As such, it may have diagnostic utility in confirming hematolymphoid lineage in cases that are negative for CD45. Aberrant CD43 expression has been described in non-hematopoietic tumors, although literature data on this topic is variable and sometimes contradictory. To clarify and expand on existing literature findings, we evaluated CD43 expression by immunohistochemistry (IHC) in a large cohort (307) of non-hematopoietic neoplasms, including poorly differentiated malignancies. METHODS: 17 tissue microarrays and sections from 19 individual cases were stained with CD43 (clone DF-T1) monoclonal antibody. The proportion of positive cells, stain localization (nuclear, cytoplasmic or membranous), and intensity (compared to internal leukocyte controls) were recorded in all cases. RESULTS: There were 98/307 (32%) positive cases, that showed focal weak nuclear staining in 1-25% of cells, including 23/25 (92%) pancreatic ductal adenocarcinomas; 31/34 (91%) breast invasive ductal carcinomas; 13/15 (87%) papillary thyroid carcinomas; 3/4 (75%) follicular thyroid carcinomas; 6/15 (40%) renal cell carcinomas; 9/28 (32%) lung adenocarcinomas; 1/13 (8%) lung squamous cell carcinomas (SCCs); 2/8 (25%) prostate adenocarcinomas; 8/62 (13%) colon adenocarcinomas; and 2/21 (10%) neuroendocrine neoplasms. None of the positive cases demonstrated strong, membranous CD43 expression comparable to that seen in background mature lymphocytes or segmented neutrophils. Negative cases included 11 cervical SCCs, 12 cervical adenocarcinomas, 19 urothelial carcinomas, 10 lung small cell carcinomas, 11 sarcomas, and 19 poorly differentiated carcinomas from various tissue sites. CONCLUSIONS: In our cohort, most non-hematopoietic neoplasms are negative for CD43 expression, with a subset showing focal, weak nuclear positivity. This data indicates that uniform and strong membranous staining appears to be specific to hematopoietic neoplasms.

Proliferation centers in bone marrows involved by chronic lymphocytic leukemia/small lymphocytic lymphoma: a clinicopathologic analysis.

OBJECTIVES: Proliferation centers (PCs) are a characteristic finding in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) lymph nodes, and their presence and extent in this site are not currently felt to be related to clinical course. In contrast, detailed clinicopathologic analyses of bone marrow (BM) PCs have not been previously reported. METHODS: The PCs in 88 CLL/SLL BMs from 45 patients (pts) were graded (0-4) and were correlated with other morphologic, immunophenotypic, cytogenetic, and laboratory features. RESULTS: Proliferation centers were present in 69 BMs (78%) from 32 pts (71%) and were distinct/prominent (grades 2-4) in 21 pts (47%), with the latter more commonly found in follow-up BMs (1/7 diagnostic BMs vs 49/81 follow-up BMs; P=.04). When present, PCs were most commonly graded as distinct nodules easily visible on ×10. No relationships were identified between PCs and any complete blood count parameter, serum lactate dehydrogenase or IgG levels, degree or pattern of BM involvement, blood morphology, CD38 and FMC7 expression by flow cytometry, or fluorescence in situ hybridization results, when the first encountered BM was considered for each patient. CONCLUSIONS: This represents the first detailed analysis of PCs in CLL/SLL BMs. In our tertiary center, PCs were seen frequently, in approximately three-fourths of cases. There were no statistical associations identified between PCs and cytogenetic, immunophenotypic, or other laboratory and morphologic findings.

Immunophenotypes of Chronic Myelomonocytic Leukemia (CMML) Subtypes by Flow Cytometry: A Comparison of CMML-1 vs CMML-2, Myeloproliferative vs Dysplastic, De Novo vs Therapy-Related, and CMML-Specific Cytogenetic Risk Subtypes.

OBJECTIVES: We sought to immunophenotype blasts, monocytes, and granulocytes in chronic myelomonocytic leukemias (CMMLs) and compare CMML subtypes, to identify if significant antigen expression differences existed. METHODS: Bone marrow blasts, monocytes, and granulocytes from CMML subgroups (n = 30; World Health Organization types 1/2, proliferative/dysplastic, therapy related/de novo, and low/intermediate/high cytogenetic risk) were immunophenotypically compared by flow cytometry with 10 nonneoplastic control marrows. RESULTS: Aberrancies were present in blasts of 26 (87%) of 30 CMMLs (26 diagnostic; four follow-up) and six (60%) of 10 controls (P = .089), monocytes of 28 (93%) of 30 CMMLs and six (60%) of 10 controls (P = .026), and granulocytes of eight (28%) of 29 CMMLs and zero of 10 controls (P = .166). Underexpression of CD14 and CD15 on monocytes was more common in CMMLs compared with controls (P = .008 and P = .043). Statistical analysis showed no significant difference in antigen expression between the CMML subgroups on blasts or monocytes; granulocytes demonstrated more common HLA-DR expression in CMML-2 vs CMML-1. CONCLUSIONS: These findings confirm heterogeneity within CMML subgroups and find no specific qualitative or quantitative findings characteristic of a subgroup.