Chronic Myelomonocytic Leukemia: Natural History and Prognostic Determinants

Tefferi, Ayalew; Hoagland, H. Clark; Therneau, Terry M.; Pierre, Robert V.

doi:10.1016/s0025-6196(12)61287-7

Cited by 80 publications

(43 citation statements)

References 31 publications

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“…Several authors have suggested the utility of cytochemical stains for nonspecific esterase (eg naphtyl butyrate esterase) for the purpose of highlighting the increased number of monocytes present in bone marrow aspirates. 1,6,28,29 However, no adequate information is available concerning the diagnostic value of such approach to confirm a diagnosis of CMML, and its ability to provide a way for separating CMML from other morphologically similar myeloid neoplasms, particularly in cases when peripheral blood results are not available.…”

Section: Cytogenetic Resultsmentioning

confidence: 99%

“…1 To overcome this difficulty, the use of cytochemical stains for monocytes such as naphtyl butyrate esterase, or naphtyl acetate esterase has been advocated. 1,6 The role of bone marrow biopsy in this condition is even less clear than that of the marrow aspirate. Besides the detection of an increased marrow cellularity owing to myeloid proliferation and the identification of fibrosis, additional diagnostic roles have not been explored.…”

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confidence: 99%

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Chronic myelomonocytic leukemia: the role of bone marrow biopsy immunohistology

et al. 2006

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The World Health Organization criteria for diagnosing chronic myelomonocytic leukemia (CMML) are largely based on findings observed in the peripheral blood and bone marrow aspirate. A specific diagnostic role for the bone marrow biopsy has not been adequately explored. We examined whether bone marrow biopsy supplemented by immunohistochemistry may be helpful in distinguishing CMML from cases of chronic myelogenous leukemia and atypical chronic myeloid leukemia (aCML). We immunostained 25 cases of CMML with paraffin reactive antibodies which included CD68 (KP1), CD68R (PG-M1), and CD163, and compared the results with those observed in six cases of chronic myelogenous leukemia and in three cases of atypical CML. In addition, we examined whether CD34 immunohistochemistry could be useful in separating cases of CMML with less than 10% blasts (type-1) from cases of CMML with blasts accounting for 10-19% (type-2), and cases of CMML in acute transformation to acute myeloid leukemia (blastsZ20%). The presence of nodules of plasmacytoid monocytes was investigated by CD123 staining. CD42b was used to highlight abnormal megakaryocytes. Our results demonstrate significant differences between the groups. CD34 analysis allowed separating CMML type-1 from type-2 and the former from CMML in acute transformation. CD123-positive plasmacytoid monocyte nodules were found only in CMML and not in the other two disease groups. Overlap between CMML and the other two groups were observed with CD68 immunostaining. CD68R was more restricted to bone marrow macrophages and monocytes than CD68, but the differences between CMML and chronic myelogenous leukemia or atypical CML were still not significant. Although CD42b immunostaining facilitated the detection of dwarf megakaryocytes often present in CMML, the distinction between those and the small forms seen in chronic myelogenous leukemia was still problematic.

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Section: Cytogenetic Resultsmentioning

confidence: 99%

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confidence: 99%

Chronic myelomonocytic leukemia: the role of bone marrow biopsy immunohistology

et al. 2006

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“…Studies looking at the outcome of chronic myelomonocytic leukemia patients, performed at various time points along the evolution of the current chronic myelomonocytic leukemia classification scheme, have variably focused on survival or progression to acute myeloid leukemia as end points; 8,9,[37][38][39] in our study, we used time-to-progression analysis to evaluate factors associated with acute myeloid leukemia evolution. Although a potential bias in the follow-up of chronic myelomonocytic leukemia cases with aggressive features (such as increased WBC or blasts) could have influenced the exact time that acute myeloid leukemia progression was detected, review of the medical records revealed similar followup intervals among the chronic myelomonocytic leukemia patients who progressed vs those who did not progress (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6] Chronic myelomonocytic leukemia progresses to acute myeloid leukemia in up to one third of cases. [7][8][9] Acute myeloid leukemia arising in a patient with a history of chronic myelomonocytic leukemia is currently classified in the 2008 WHO classification as acute myeloid leukemia with myelodysplasiarelated changes. This aggressive subtype comprises a heterogeneous group of acute myeloid leukemia cases that either arise from a previous myelodysplastic syndrome or myelodysplastic syndrome/ myeloproliferative neoplasm (including chronic myelomonocytic leukemia), bear an myelodysplastic syndrome-related cytogenetic abnormality, or demonstrate significant multilineage dysplasia.…”

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confidence: 99%

Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia

Courville

Kourda

et al. 2013

Modern Pathology

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Acute myeloid leukemia arising from chronic myelomonocytic leukemia is currently classified as acute myeloid leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic myelomonocytic leukemia who progressed to acute myeloid leukemia. We compared the clinicopathologic and genetic features of these cases with 180 patients with de novo acute myeloid leukemia and 34 patients with acute myeloid leukemia following myelodysplastic syndromes. We also examined features associated with progression from chronic myelomonocytic leukemia to acute myeloid leukemia by comparing the progressed chronic myelomonocytic leukemia cases with a cohort of chronic myelomonocytic leukemia cases that did not transform to acute myeloid leukemia. Higher white blood cell count, marrow cellularity, karyotype risk score, and Revised International Prognostic Scoring System score were associated with more rapid progression from chronic myelomonocytic leukemia to acute myeloid leukemia. Patients with acute myeloid leukemia ex chronic myelomonocytic leukemia were older (Po0.01) and less likely to receive aggressive treatment (P ¼ 0.02) than de novo acute myeloid leukemia patients. Most cases showed monocytic differentiation and fell into the intermediate acute myeloid leukemia karyotype risk group; 55% had normal karyotype and 17% had NPM1 mutation. Median overall survival was 6 months, which was inferior to de novo acute myeloid leukemia (17 months, P ¼ 0.002) but similar to post myelodysplastic syndrome acute myeloid leukemia. On multivariate analysis of all acute myeloid leukemia patients, only age and karyotype were independent prognostic variables for overall survival. Our findings indicate that acute myeloid leukemia following chronic myelomonocytic leukemia displays aggressive behavior and support placement of these cases within the category of acute myeloid leukemia with myelodysplasia-related changes. The poor prognosis of these patients may be related to an older population and lack of favorable-prognosis karyotypes that characterize many de novo acute myeloid leukemia cases.

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“…20,21 It has a high rate of transformation to acute leukemia and no significant improvement in disease course with chemotherapy. [21][22][23][24] Zang et al published a case series of 21 patients with CMML. In all, 12 patients received transplants from HLA-matched sibling, three from HLA nonidentical related donor and six patients received unrelated donor transplants.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic transplantation: a therapeutic option for myelofibrosis, chronic myelomonocytic leukemia and Philadelphia-negative/BCR-ABL-negative chronic myelogenous leukemia

Mittal

Saliba

Giralt

et al. 2004

Bone Marrow Transplant

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Summary:The role of allogeneic transplantation for myeloproliferative diseases other than chronic myeloid leukemia is not well established. In all, 20 patients with a median age of 51 years underwent allogeneic hematopoietic stem cell transplantation (HSCT) for myelofibrosis (n ¼ 5), chronic myelomonocytic leukemia (CMML) (n ¼ 8) and Philadelphia (Ph) chromosome-negative/BCR-ABL-negative chronic myeloid leukemia (CML) (n ¼ 7) in our institution. Patients who developed acute leukemia prior to HSCT were excluded from this analysis. A total of 15 patients received related and five patients received unrelated donor transplants. One patient failed to engraft. After a median follow-up of 17.5 months, actuarial survival at 2 years was 47% (95% CI 2%-67%), and disease-free survival 37% (95% CI 17-58%). Allogeneic transplantation may provide a therapeutic option for patients with myelofibrosis, CMML and Ph chromosomenegative/BCR-ABL-negative CML.

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Chronic Myelomonocytic Leukemia: Natural History and Prognostic Determinants

Cited by 80 publications

References 31 publications

Chronic myelomonocytic leukemia: the role of bone marrow biopsy immunohistology

Chronic myelomonocytic leukemia: the role of bone marrow biopsy immunohistology

Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia

Allogeneic transplantation: a therapeutic option for myelofibrosis, chronic myelomonocytic leukemia and Philadelphia-negative/BCR-ABL-negative chronic myelogenous leukemia

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