Chronic Myelomonocytic Leukemia (CMML) with More Than 15% of Ring Sideroblasts in Bone Marrow: An Overlapping Disorder Between CMML and Refractory Anemia with Ring Sideroblasts.

Abstract Abstract 290 The main diagnostic criteria for chronic myelomonocytic leukemia (CMML), a heterogeneous disorder sharing features of myelodysplastic syndromes (MDS) and chronic myeloproliferative disorders, is the existence of a sustained absolute monocyte count in peripheral blood (PB) above 1 × 109/L. On the other hand, the presence of more than 15% ring sideroblasts (RS) in bone marrow (BM) is a well recognized morphological feature of dyserithropoiesis and, in the absence of blasts in PB and less than 5% blasts in BM, is diagnostic of refractory anemia with ring sideroblasts (RARS) with or without multilineage dysplasia. In FAB as well as in WHO classification systems for myeloid neoplasms those cases presenting with both an absolute monocyte count in PB above 1 × 109/L and more than 15% RS in BM are diagnosed of CMML but the preeminence given to the monocyte count in PB over the proportion of RS in BM is not evidence-based. The main purpose of this study was to assess the clinical and biological characteristics and outcome [overall survival (OS) and acute leukemic (AL) evolution] of a series of 77 patients diagnosed of CMML by FAB and WHO criteria who had more than 15% RS in BM at presentation (CMML-RS) and to compare them with those of a series of 417 patients with CMML with less than 15% RS (classical CMML) and those of a series of 178 patients with classical RARS (38 patients with and 140 patients without multilineage dysplasia). Comparisons of proportions and ranks of variables between different groups were performed by chi square or Mann-Whitney-U tests as appropriate. Actuarial curves of OS and risk of AL evolution were built by Kaplan-Meier method and differences between curves compared with log-rank tests. Multivariate analyses of OS and risk of AL evolution were performed by Cox proportional hazards regression method. Patients with CMML-RS had lower hemoglobin level (P=0.008), lower absolute counts of leukocytes (P<0.001), neutrophils (P=0.002), and monocytes (P<0.001), higher platelet count (P<0.001), lower proportion of blasts in PB (P=0.015) and BM (P=0.035), and higher serum level of ferritin (P<0.001) and LDH (P=0.06) than patients with classical CMML. Patients with CMML-RS had significantly better OS than patients with classical CMML (median, 79 mo and 26 mo respectively; P<0.001; Figure) as well as lower risk of AL evolution (cumulative proportion at 5 yr, 7% and 20% respectively; P=0.07). Further, the beneficial prognostic relevance of the proportion of RS in BM on OS was maintained in multivariate analyses (P<0.001). In marked contrast, OS (median, 64 mo; Figure) and risk of AL evolution (cumulative proportion at 5 yr, 9%) of patients with classical RARS were closely similar to those observed in patients with CMML-RS (P>0.90). Patients with classical RARS were more anemic (P=0.001), had lower absolute counts of leukocytes (P<0.001), neutrophils (P=0.01), and monocytes (P<0.001), higher platelet count (P=0.002), lower proportion of blasts in PB (P=0.01) and BM (P<0.001), and lower serum level of ferritin (P=0.01) and LDH (P=0.11) than patients with CMML-RS. To avoid the potential interference in the analyses of disparities in the proportion of blasts in BM in the different groups of patients all the analyses were repeated excluding from all the groups those cases with 5% or more blasts in BM. Fifty-three patients with CMML-RS, 245 with classical CMML, and all 178 with classical RARS were evaluable for these sub-analyses. The results obtained were similar to those in the overall series of patients (data not showed). To sum up, all these results show that the proportion of RS in BM is a much powerful prognostic indicator than absolute monocyte count in PB in CMML and demonstrate that the presence of a proportion of RS greater than 15% in BM in patients with CMML defines a subset of patients that clearly differ in their biological characteristics from classical CMML and classical RARS. CMML-RS has a clinical course very close to that of classical RARS and markedly better than classical CMML. These data strongly suggest that CMML-RS is an overlapping syndrome between CMML and RARS. For clinical purposes patients with >1 × 109 monocytes/L in PB and >15% RS in BM should be better classified as RARS than as CMML. The WHO classification needs to be revisited to account for those findings. Disclosures: No relevant conflicts of interest to declare.

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Ruxolitinib Treatment Outcome In a Patient With Secondary Chronic Myelomonocytic Leukemia

Blood ◽

10.1182/blood.v122.21.5230.5230 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5230-5230

Author(s):

Dina Istasi ◽

Sylvain Chantepie ◽

Edouard Cornet ◽

Veronique Salaun ◽

Michele Malet ◽

...

Keyword(s):

Bone Marrow ◽

Platelet Count ◽

Conflicts Of Interest ◽

White Blood Cells ◽

Chronic Myelomonocytic Leukemia ◽

Rapid Decline ◽

Published Data ◽

Rapid Progression ◽

Monocyte Count ◽

Myelomonocytic Leukemia

Abstract Chronic myelomonocytic leukemia ( CMML) is a de novo myelodysplastic/myeloproliferative disease with an unfavorable prognosis. Secondary CMML cases are rare and sporadically reported. Published data have shown that development of monocytosis in patients during the course of PMF or MDS is associated with poor prognosis (M.A. Elliott, Leukemia Research, 31 (2007). Essential thrombocythemia (ET) is an indolent myeloproliferative disorder characterized by long symptom-free intervals. Uncommonly, few patients with ET may develop bone marrow (BM) fibrosis which to be distinguished from cases with early PMF accompanied by thrombocytosis. Progression to acute leukemia or myelodysplastic syndrome (MDS) occurs in < 5% of patients and is likely related to previous cytotoxic therapy. We report here a rare case of a patient with ET who developed BM fibrosis and rapidly progressed to a secondary myelomonocytic leukemia. A 54 years old female patient, diagnosed with ET in 2003, as she presented a persistent isolated high platelet count of 700 G/L, with normal white blood cells (WBCs): 8 G/L, hemoglobin (hb): 15 g/dl, monocytes: 0.5 G/L and no splenomegaly. She was treated with Anagrelide 1.5 -2 mg daily due to intolerance to hydroxyurea. No major event has been declared during the last 10 years and a median platelet count of 450 G/L. In January 2013, a routine check-up showed leukocytosis (WBCs: 25 G/L), slight anemia (hb: 11.6 g/dl), with relative thrombocytopenia, 266 G/L, monocytosis: 2 G/L with 3% circulating blasts and a palpable spleen. The bone marrow biopsy revealed BM fibrosis grade III and 7% of blasts. Progression to secondary myelofibrosis was declared and treatment with hydroxyurea was initiated to control peripheral blood counts prior to transplantation. Treatment with ruxolitinib started in May, at a dose of 20 mg bid due to failure of blood count reduction with hydroyurea. A rapid decline in WBCs count to 3 G/L was achieved but with sustained median monocytosis of 1.4 G/L. The patient developed marked anemia (7.5 g/dl) as well as thrombocytopenia (13 G/L) and ruxolitinib was interrupted by the end of June 2013. Within 15 days, the patient showed rapid progression, her WBCs count attained 105 G/L, anemia and thrombocytopenia persisted. The absolute monocyte count increased up to 66 G/L with marked dysplastic features and morphological shifting to aspects compatible with overt secondary myelomonocytic leukemia in both blood and bone marrow smears, 3% circulating and 8% bone marrow blastes (WHO criteria for CMML diagnosis). Molecular studies showed the presence of JAK2 V617F allele burden at 66% and absence of BCR/ABL transcript. Only two mitosis, with an unidentified additional marker were obtained on chromosome analysis. Unfortunately, the patient died 2 weeks later. This observation shows the adverse prognostic development of monocytosis in ET which is similar to that published in PMF in 10 patients (Leonardo Boiocchi, Modern pathology, 2013), thus requiring particular attention in the treatment of these patients. As chromosomal analysis was unavailable at diagnosis, we weren’t able to prove the presence of clonal heterogeneity, a concept developed recently to explain the mechanism of development of two different diseases. Ruxolitinib is an inhibitor of JAK1 and JAK2 resulting in a dramatic decrease in cytokines and growth factors that are important for hematopoiesis and growth function. Of note, in this case, ruxolitinib which was administrated for the treatment of 2ry myelofibrosis, inhibited as well the increase in monocytosis and controlled the progression of CMML evidenced by the remarkable increase in dysplastic monocytes after its interruption. To our knowledge a clinical trial is actually on going to assess if its administration can improve the outcome of patients with CMML and the optimal dose to be administrated. Disclosures: No relevant conflicts of interest to declare.

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Molecular similarity between myelodysplastic form of chronic myelomonocytic leukemia and refractory anemia with ring sideroblasts

Haematologica ◽

10.3324/haematol.2012.071506 ◽

2012 ◽

Vol 98 (4) ◽

pp. 576-583 ◽

Cited By ~ 7

Author(s):

V. Gelsi-Boyer ◽

N. Cervera ◽

F. Bertucci ◽

M. Brecqueville ◽

P. Finetti ◽

...

Keyword(s):

Molecular Similarity ◽

Chronic Myelomonocytic Leukemia ◽

Refractory Anemia ◽

Ring Sideroblasts ◽

Myelomonocytic Leukemia

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Myelodysplastic/Myeloproliferative Neoplasms

Hematology ◽

10.1182/asheducation-2011.1.264 ◽

2011 ◽

Vol 2011 (1) ◽

pp. 264-272 ◽

Cited By ~ 29

Author(s):

Mario Cazzola ◽

Luca Malcovati ◽

Rosangela Invernizzi

Keyword(s):

Clinical Laboratory ◽

Myeloproliferative Neoplasms ◽

Chronic Myelomonocytic Leukemia ◽

World Health ◽

Refractory Anemia ◽

Molecular Diagnostic ◽

Juvenile Myelomonocytic Leukemia ◽

Lymphoid Tissues ◽

Ring Sideroblasts ◽

Myelomonocytic Leukemia

Abstract According to the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues, myelodysplastic/myeloproliferative neoplasms are clonal myeloid neoplasms that have some clinical, laboratory, or morphologic findings that support a diagnosis of myelodysplastic syndrome, and other findings that are more consistent with myeloproliferative neoplasms. These disorders include chronic myelomonocytic leukemia, atypical chronic myeloid leukemia (BCR-ABL1 negative), juvenile myelomonocytic leukemia, and myelodysplastic/myeloproliferative neoplasms, unclassifiable. The best characterized of these latter unclassifiable conditions is the provisional entity defined as refractory anemia with ring sideroblasts associated with marked thrombocytosis. This article focuses on myelodysplastic/myeloproliferative neoplasms of adulthood, with particular emphasis on chronic myelomonocytic leukemia and refractory anemia with ring sideroblasts associated with marked thrombocytosis. Recent studies have partly clarified the molecular basis of these disorders, laying the groundwork for the development of molecular diagnostic and prognostic tools. It is hoped that these advances will soon translate into improved therapeutic approaches.

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Interaction between ring sideroblasts and treatment with hypomethylating agents (HMA) in patients with refractory anemia with ring sideroblasts.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18559 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18559-e18559

Author(s):

Rama Nanah ◽

Darci Zblewski ◽

Rong He ◽

Phuong L. Nguyen ◽

Naseema Gangat ◽

...

Keyword(s):

Bone Marrow ◽

Myeloid Leukemia ◽

Median Overall Survival ◽

Multivariate Analyses ◽

Median Number ◽

Refractory Anemia ◽

Myeloid Neoplasms ◽

Kaplan Meier ◽

Ring Sideroblasts ◽

Number Of Cycles

e18559 Background: Myelodysplastic syndromes (MDS) are a group of myeloid neoplasms defined by ineffective hematopoiesis, dysplastic morphologic features, and variable risks of progression to acute myeloid leukemia (AML). Refractory anemia with ring sideroblasts (RARS) is a subtype of MDS defined by < 5% basts and > 15% ring sideroblasts (per 2008 WHO). Because RARS is a lower risk disease which does not frequently require HMA therapy, very little is known about the effects of HMA on RARS. Methods: A total of 1325 MDS patients’ data from 1993-2016 at Mayo Clinic were reviewed after appropriate IRB approval was obtained. All cases had their bone marrow slides reviewed at our center. Patients were considered for our study if they received HMA for their RARS. Response was identified based on MDS IWG 2006 criteria. Prognostic factors were analyzed by univariate and multivariate analyses. Survival estimates were calculated using Kaplan-Meier curves. Results: 168 of the initial 1325 patient were RARS (14%); only 14 (8%) were treated with HMA. Median age was 72 years (range, 51-85); half were males, with median overall survival of 91.3 months. The median number of ring sideroblasts (RS) at diagnosis was 40% (range 10-85%). Of the 14 patients, 11 (79%) received azacitidine (AZA), 2 (14%) decitabine (DAC) and one received both (7%). The median number of cycles for AZA was 6.5 (range, 2-28) vs 6 cycles for DAC (range, 1-24). Of the 14 patients receiving HMA, only 3 responded (21%) achieving hematologic improvement. All 3 responders received AZA. 6 of the 14 RARS patients (43%) had their bone marrow biopsy repeated after HMA therapy, 3 of whom were among the responders to AZA therapy and 3 were non-responders. In 5 patients, ring sideroblasts decreased after HMA therapy by a median of 15% (range 0-80); they remained the same in 1 patient; one patient who had developed AML had a decrease in RS from 85% to 5%. Conclusions: RARS is a low-risk subtype of MDS that is infrequently treated with HMA (8% in our study). Response rate to HMA (21%) was inferior to known rates in MDS. HMA therapy seems to decrease the number of ring sideroblasts irrespective of response. RARS patients should be treated on clinical trials if available.

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Diagnostic Approach To Oligomonocytic Chronic Myelomonocytic Leukemia

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.245 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S112-S112

Author(s):

J Muldoon ◽

M Czader

Keyword(s):

Bone Marrow ◽

Peripheral Blood ◽

Molecular Genetic ◽

Chronic Myelomonocytic Leukemia ◽

Differential Count ◽

Normocytic Anemia ◽

Molecular Testing ◽

Monocyte Count ◽

Diagnostic Threshold ◽

Myelomonocytic Leukemia

Abstract Casestudy: Pathologic diagnosis of chronic myelomonocytic leukemia (CMML) is typically straightforward with the majority of patients presenting with persistent monocytosis (>1x109/L, >=10%) and bone marrow dysplasia. The diagnosis may be challenging in patients with unusual features such as lack pf peripheral blood monocytosis and non-diagnostic bone marrow morphology. In this abstract, we present a 67-year-old female with a 5-year history of anemia of unclear etiology. At the time of initial presentation, the laboratory work-up of normocytic anemia was non- contributory, the bone marrow was reported as normocellular with maturing trilineage hematopoiesis and no significant dysplasia. Over the course of the disease, the peripheral blood monocyte count fluctuated from 11% to 18% with absolute monocyte count ranging from 0.4 to 0.7x109/L. The most recent bone marrow was markedly hypercellular with increased trilineage hematopoiesis with left shift, dysgranulopoiesis and dysmegakaryopoiesis. Blasts (including promonocytes) constituted 10% of the differential count and were immunophenotypically abnormal with uniform expression of CD117, dim to negative CD13, and partial CD15. Monocytes were elevated at 12% and were strongly positive for CD64 and partially for CD14. They were negative for CD16 consistent with classical monocytes, and showed partial loss of CD13. The karyotype was normal. Molecular testing revealed TET2, RELN and SRSF2 mutations at high allelic frequencies. This case illustrates a value of flow cytometric immunophenotyping and molecular genetic studies in diagnosing challenging cases of CMML. While the patient’s absolute monocyte count remained below the diagnostic threshold of 1x109/L throughout the course of the disease, peripheral blood and bone marrow monocytes showed skewed classical immunophenotype, immunophenotypic abnormalities of myeloid series and high allelic frequency mutations. These findings should raise a differential diagnosis of oligomonocytic CMML, even when morphologic abnormalities and monocyte count threshold are not diagnostic.

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Dysmyelopoietic syndrome: sequential clinical and cytogenetic studies

Blood ◽

10.1182/blood.v55.4.636.bloodjournal554636 ◽

1980 ◽

Vol 55 (4) ◽

pp. 636-644

Author(s):

RA Streuli ◽

JR Testa ◽

JW Vardiman ◽

U Mintz ◽

HM Golomb ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Chronic Myelomonocytic Leukemia ◽

Refractory Anemia ◽

Banding Technique ◽

Cytogenetic Studies ◽

Carcinogenic Agents ◽

Cytogenetic Analyses ◽

Myelomonocytic Leukemia ◽

French American British

Clinical and cytogenetic studies were done on 8 patients with dysmyelopoietic syndrome: 6 of these patients had refractory anemia with an excess of blasts (RAEB), and 2 patients had chronic myelomonocytic leukemia (CMML) according to the French-American-British classification. The ages of these 8 patients (3 female and 5 male) ranged from 45 to 70 yr (median, 61.5 yr). Seven of the 8 patients died 3–86 mo (median, 11 mo) after the onset of symptoms of hemorrhage or infections. Cytogenetic studies of bone marrow cells with the Q-banding technique showed clonal karyotypic abnormalities in 7 of the 8 patients (87.5%). Five of the 7 chromosomally abnormal patients had very complex karyotypes; all 7 patients, however, had at least 1 of 4 specific changes: -5 (or 5Q-), -7, +8, and +21. Three of the 7 patients with abnormal karyotypes had had some exposure to potential mutagenic/carcinogenic agents. Five of the 7 patients had serial cytogenetic analyses, 4 of which showed evolution of the karyotype to further complexity; in 2 cases, this coincided with the evolution of the disease into acute leukemia. The median survival time of patients whose initial cytogenetic samples showed both normal and abnormal metaphases was more than twice that of patients who had only abnormal metaphases initially (12 mo versus 4.5 mo).

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Survival and Prognosis in World Health Organization Defined Chronic Myelomonocytic Leukemia- A Mayo Clinic Series of 227 Patients

Blood ◽

10.1182/blood.v120.21.3790.3790 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3790-3790

Author(s):

Mrinal M. Patnaik ◽

Curtis A Hanson ◽

Janice M Hodnefield ◽

Ryan A Knudson ◽

Rhett P Ketterling ◽

...

Keyword(s):

Risk Factors ◽

Bone Marrow ◽

Platelet Count ◽

Risk Stratification ◽

Risk Model ◽

Chronic Myelomonocytic Leukemia ◽

Leukemic Transformation ◽

Immature Myeloid Cells ◽

Independent Risk Factors ◽

Myelomonocytic Leukemia

Abstract Abstract 3790 Background: Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder characterized by: persistent peripheral blood (PB) monocytosis (>1 × 10(9)/L), absence of BCR-ABL1 fusion, absence of rearrangement of the PDGFRA/B genes, <20% bone marrow (BM) & PB blasts, and dysplasia involving one or more myeloid cell lines. It is clinically considered to be an overlapping syndrome with myelodysplastic and myeloproliferative features. The natural history and prognostic features of CMML are not well defined with the MD Anderson prognostic score (MDAPS) and the Spanish risk stratification by cytogenetics being the two major prognostic tools currently being used in clinical practice. Methods: 227 patients with WHO defined CMML were seen at the Mayo Clinic from 1997 through 2007. All patients underwent bone marrow (BM) examination and cytogenetic evaluation at diagnosis. We evaluated the prognostic relevance of several clinical and laboratory parameters including those previously identified by the MDAPS (Blood 2002;99:840) and the Spanish cytogenetic risk stratification (Haematologica 2011;96:375). Results: Among the 227 study patients, 153 (67%) were males and median age was 71 years (range, 17–90 years). There were 192 (85%) patients with CMML-1 & the remainder had CMML-2. At a median follow-up of 15 months, 166 (73%) deaths and 33 (14.5%) leukemic transformations were documented. Median survivals were 22 months for CMML-1 and 14 months for CMML-2. In univariate analysis, significant risk factors for survival included decreased hemoglobin level, decreased platelet count and increased levels of white blood cells (WBC), absolute neutrophils (ANC), absolute monocytes (AMC), absolute lymphocytes (ALC), PB blasts, BM blasts and presence of circulating immature myeloid cells (IMC; inclusive of PB blasts). However, on multivariable analysis that included the aforementioned Spanish cytogenetic risk stratification, only increased AMC (>10 × 10(9)/L, RR 2.5, 95% CI 1.7–3.8), presence of circulating IMC (RR 2.0, 95% CI 1.4–2.7), decreased hemoglobin (<10 g/dL; RR 1.6, 99% CI 1.2–2.2), and decreased platelet count (<100 × 10(9)/L; RR 1.4, 99% CI 1.0–1.9) retained significance. Using these four independent risk factors, we prepared a new prognostic risk model that performed better than both the MDAPS and the Spanish cytogenetic risk models (Figure). The Mayo risk model was also predictive of leukemic transformation: high risk RR 4.9 (95% CI 1.9–12.8) and intermediate risk RR 2.6 (1.1–5.9). Individual parameters of independent significance for leukemic transformation included PB blast count and AMC >10 × 10(9)/L. Conclusions: Absolute monocyte count is the strongest predictor of survival in CMML. Other independent risk factors include circulating immature myeloid cells, anemia and thrombocytopenia. A risk model based on these four risk factors is effective in predicting both overall and leukemia-free survival and outperforms both the MDAPS and risk stratification by cytogenetics. Disclosures: No relevant conflicts of interest to declare.

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Dysmyelopoietic syndrome: sequential clinical and cytogenetic studies

Blood ◽

10.1182/blood.v55.4.636.636 ◽

1980 ◽

Vol 55 (4) ◽

pp. 636-644 ◽

Cited By ~ 65

Author(s):

RA Streuli ◽

JR Testa ◽

JW Vardiman ◽

U Mintz ◽

HM Golomb ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Chronic Myelomonocytic Leukemia ◽

Refractory Anemia ◽

Banding Technique ◽

Cytogenetic Studies ◽

Carcinogenic Agents ◽

Cytogenetic Analyses ◽

Myelomonocytic Leukemia ◽

French American British

Abstract Clinical and cytogenetic studies were done on 8 patients with dysmyelopoietic syndrome: 6 of these patients had refractory anemia with an excess of blasts (RAEB), and 2 patients had chronic myelomonocytic leukemia (CMML) according to the French-American-British classification. The ages of these 8 patients (3 female and 5 male) ranged from 45 to 70 yr (median, 61.5 yr). Seven of the 8 patients died 3–86 mo (median, 11 mo) after the onset of symptoms of hemorrhage or infections. Cytogenetic studies of bone marrow cells with the Q-banding technique showed clonal karyotypic abnormalities in 7 of the 8 patients (87.5%). Five of the 7 chromosomally abnormal patients had very complex karyotypes; all 7 patients, however, had at least 1 of 4 specific changes: -5 (or 5Q-), -7, +8, and +21. Three of the 7 patients with abnormal karyotypes had had some exposure to potential mutagenic/carcinogenic agents. Five of the 7 patients had serial cytogenetic analyses, 4 of which showed evolution of the karyotype to further complexity; in 2 cases, this coincided with the evolution of the disease into acute leukemia. The median survival time of patients whose initial cytogenetic samples showed both normal and abnormal metaphases was more than twice that of patients who had only abnormal metaphases initially (12 mo versus 4.5 mo).

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Prognostic Factors in Chronic Myelomonocytic Leukemia: A Retrospective Analysis of 41 Patients

Blood ◽

10.1182/blood.v112.11.4279.4279 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4279-4279

Author(s):

Bobin Chen ◽

Xiaoping Xu ◽

Yan Ma ◽

Xiaoqin Wang ◽

Guowei Lin

Keyword(s):

Bone Marrow ◽

Prognostic Factors ◽

Prognostic Factor ◽

Survival Time ◽

Neutrophil Count ◽

Peripheral Blood ◽

Lymphocyte Count ◽

Chronic Myelomonocytic Leukemia ◽

Monocyte Count ◽

Myelomonocytic Leukemia

Abstract Purpose To investigate clinical characteristic and prognostic factors for chronic myelomonocytic leukemia (CMML). Methods Retrospective cohort study was used in the study. Information for CMML patients was collected, including symptoms, CBC, results of bone marrow aspire and pathology, cytogenetic. All patients were followed up regularly. Analysis of survival and prognostic factors was performed by Kaplan-Merier cure, log rank test and Cox regression model. Results Forty-one cases were diagnosed as CMML, including 27 male and 14 female patients. Median WBC was 13.7× 109/L. Five patients had leukocytopenia(1.92- 3.46×109/L). Median monocyte count in the peripheral blood was 2.13×109/L, but lower monocyte count (<1×109/L) occurred in 8 patients. All patients presented with bone marrow dysplasia, and most showed hyperplasia, except 3 cases. Abnormal chromosome was detected in 34% cases. Median survival time was 20 months, and there were no difference of survival duration between CMML-1 and CMML-2. Univariate analysis showed that age (> 60 yrs), neutrophil count (<2.0′109/L), lymphocyte count (<1.0′109/L), mature monocyte count (35′109/L) and anemia (Hb< 60g/L) were associated with poor prognosis for CMML. There was no statistical significance in LDH, gender, abnormal chromosome for survival time. Only lymphocyte count and neutrophil count in peripheral blood were independent prognostic factor for CMML after Multivariate analysis. Conclusion CMML mainly occur in elderly patients. Although most patients have leukocytosis and monocytosis at diagnosis, few case shows leucopenia and monocytopenia. Median survival time for CMML is 20 months. Age, neutrophil, lymphocyte and monocyte count, severe anemia are related to CMML prognosis. Neutropenia and lymphopenia in peripheral blood are independent prognostic factor for CMML.

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Unusual Response of Acute Monocytic Leukemia to Dandelion Root Extract

Blood ◽

10.1182/blood.v118.21.4288.4288 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4288-4288

Author(s):

Caroline Hamm ◽

Sindu M. Kanjeekal

Keyword(s):

Bone Marrow ◽

Flow Cytometry ◽

Platelet Count ◽

Bone Marrow Biopsy ◽

Chronic Myelomonocytic Leukemia ◽

Acute Monocytic Leukemia ◽

Root Extract ◽

Monocytic Leukemia ◽

Monocytic Cells ◽

Myelomonocytic Leukemia

Abstract 4288 Seventy year old man presented to Windsor Regional Cancer Centre with fever and pancytopenia on June 24, 2009. Presenting CBC was as follows: WBC 47.8:Ne 0.3, Ly 0.06, Mo 0.62, Meta 0.01, bands 0.01; Hgb 123; Platelets 55,000. A bone marrow biopsy revealed the following: 70% cellularity with sheets of immature blast-like cells; the lesional cells were CD68 and MPO positive and negative for CD34, CD117, CD138, CD20 and CD3. Flow cytometry revealed 46% of the cells positive for CD33, Cd36, CD64, MY4, CD16, HLA-DR, CD13, CD 56, CD10, CD11b, dim CD4, MPO positive, consistent with acute monocytic leukemia. Cytogenetics were 46, XY [24]. He was given the diagnosis of acute monoblastic leukemia and was started on standard induction chemotherapy: 3 + 7 daunorubicin and ara-C. (doses). Repeat bone marrow biopsy on July 17, 2009 revealed lack of remission. This bone marrow revealed sheets of blast-like cells with 30% residual monoblast population and 4% myeloblast population. He was then treated with high dose cytarabine (3 gm / m2 q day 1, 3, 5) for one cycle. Repeat bone marrow biopsy on Aug 20, 2009 revealed non-remission with 20% residual monoblasts. At this time, it was explained to him that he would be treated in a palliative fashion only. He started low dose AraC at this time and received one 21 day course. He showed hematological recovery by September 2009. Repeat bone marrow biopsy on October 5th, 2009 showed 6% residual myeloblast and 40% monocytic population. Because of previous signals of response at our centre to dandelion root tea/ water extract, and because of his current palliative diagnosis, we mentioned dandelion root tea to him. He started this tea on his own and was followed expectantly. Another bone marrow biopsy at the end of November 2009 showed only residual monocytic population of 10 – 12 % with 79% myeloid cells showing dysplastic features consistent with chronic myelomonocytic leukemia type 2. In March 2010, his platelet count started a gradual decline. By December 29, 2010, the platelet count had dropped to 35,000 × 10 9, and a bone marrow biopsy was done to determine etiology. Bone marrow biopsy from January 25, 2011 shows features suggestive chronic myelomonocytic leukemia. This biopsy revealed monocytic cells, as well as occasional promonocytes. There was adequate megakaryoctyes, no Auer rods, no blasts. The monocytes expressed 9% of the total nucleated cells, and did not express CD56. Flow cytometry reported all normal. A diagnosis of idiopathic thrombocytopenic purpura was made and patient was started on prednisone with subsequent improvement in his platelet count. CBC on July 4, 2011, almost two years from his diagnosis of refractory M5 AML, patient’s CBC is almost normal with a white blood count of 7.5 ×10*9/L, hemoglobin of 122 g/L, platelets of 134 ×10*9/L, neutrophils of 3.6 × 10*9/L, monocytes of 1.65 × 10*9/L. His quality of life remains excellent. He continues using dandelion root tea. In view of this very exciting response and the more temporary response seen in chronic myelomonocytic leukemia, as well as the exciting findings we have seen in monocytic cells lines and tolerance in animal models, we moving into a phase I/II clinical trial examining the effect of dandelion root extract in patients with monocytic leukemias. Disclosures: No relevant conflicts of interest to declare.

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