Unusual Response of Acute Monocytic Leukemia to Dandelion Root Extract

Blood ◽  
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.

scholarly journals Chronic monocytic leukemia with transformation into acute monocytic leukemia. Clinical case

Morphologia ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 49-57
Author(s):  
L. A. Pesotskaya ◽  
A. S. Korolenko
Keyword(s):  
Bone Marrow ◽  
Clinical Case ◽  
Skin Lesions ◽  
Chronic Myelomonocytic Leukemia ◽  
Morphological Data ◽  
Unknown Etiology ◽  
Acute Monocytic Leukemia ◽  
Monocytic Leukemia ◽  
Myelomonocytic Leukemia ◽  
Rapid Transformation

Background. Chronic myelomonocytic leukemia (CML) is rarely diagnosed and it is 1 per 100 thousand adults annually, in the United States - in 4 per million people, which is about 1100 cases per year. This disease is more common for men over 60. Results. A clinical case of a rare long-term course of myelodysplastic chronic myelomonocytic leukemia (MDCMML) in a middle-aged woman with rapid transformation into acute monocytic leukemia (AMoL-M5v) with atypical fulminant course is presented. Changes in the blood test were identified accidentally during a routine examination. A retrospective analysis of the course of the patient's disease, anamnesis made it possible to draw attention to the severe course of vasculitis of unknown etiology, with a predominant lesion of the skin of the lower limbs, which required inpatient treatment (19 years ago); skin lesions in the form of transient erythema, spotty eruptions for more than 10 years, moderate cervical lymphadenopathy. According to the WHO criteria, the morphological data of the bone marrow puncture corresponded to the MD of the CML. The long course of the disease without an obvious clinical picture, neutrophil dysplasia, myeloid proliferation was atypical, which did not exclude the presence of previous oligomonocytic CML in the patient. A detailed picture of the disease appeared after a viral infection, bronchitis, antibiotic therapy. In the absence of an increase in the number of blasts in the bone marrow, in a few of them normal Auer's sticks were detected, which, according to the literature, is a rarity in CML and an unfavorable prognostic factor of rapid transformation into acute myeloid leukemia. Conclusion. Not typical for the course of acute monocytic leukemia in this case were the absence of significant blastemia and severe suppression of normal hematopoiesis with pronounced extramedular manifestations. There was febrile fever, hyperplasia of the gums, tonsils with ulcerative-necrotic changes in the oral mucosa, an increase in cervical lymph nodes in the form of packets up to 2 cm in diameter with signs of sarcomatous growth. Attention was drawn to the progression of skin lesions, which was prognostically unfavorable. Notable was the development of severe hemorrhagic syndrome without severe thrombocytopenia, significant changes in the coagulogram, as a manifestation of early severe coagulopathy. There was a spread of erythematous elements on the skin with itching, not controlled by antihistamines and corticosteroid drugs (maculopapular rashes of a pink-cyanotic color, in places of a confluent nature, small-point hemorrhages like vasculitis over the entire surface of the skin).

scholarly journals "Monocytic" Cells of Normal Blood, Schilling and Naegeli Leukemia, and Leukemic Reticuloendotheliosis in Slide Chambers

Blood ◽  
1962 ◽  
Vol 20 (4) ◽  
pp. 453-470 ◽  
Author(s):  
YALE RABINOWITZ ◽  
ROBERT SCHREK
Keyword(s):  
Blood Cells ◽  
Acute Monocytic Leukemia ◽  
Reticulum Cell ◽  
Monocytic Leukemia ◽  
Monocytic Cells ◽  
Fresh Serum ◽  
Morphology Development ◽  
And Function ◽  
Myelomonocytic Leukemia ◽  
Physiologic Data

Abstract 1. The study of living blood cells in slide chambers by phase microscopy and cinemicrography adds useful morphologic, developmental and physiologic data complementary to other methods for studying blood cells. 2. Normal monocytes were characterized by flattening in fresh serum with minimal ameboid motility, by ectoplasmic veils waving in the medium, and by transformation to fully developed macrophages in 5-7 days. 3. Cells from four patients with acute monocytic leukemia (Schilling type) showed only slight differences in morphology, development and function from normal monocytes in the slide chamber. 4. Monocytoid cells from four patients with myelomonocytic leukemia (Naegeli type), in the slide chamber, resembled those from two patients with leukemic reticuloendotheliosis in morphology, development and function, but differed from normal monocytes and cells of acute monocytic (Schilling) leukemia. The monocytoid cells were labeled "reticulum" cells with the implication that they were related to the primitive hematopoietic reticulum cell. 5. The "reticulum" cell in the slide chamber differed from the monocyte in having a coarse nuclear chromatin pattern with clumping of chromatin, larger numbers of varying sized cytoplasmic granules, less ectoplasm, development of characteristic star-shaped macrophage forms without ectoplasmic veils, and in exhibiting a considerable ameboid motility as opposed to the sluggish veil waving of the monocyte. 6. Speculation as to the significance of the "reticulum" cell has been presented with the suggestion that this cell precedes the blast cell in hematopoiesis. In Naegeli leukemia, unknown factors may cause alterations in the type of cell released from the marrow. There may also be shifts in emphasis between myeloblast and pre-myeloblast proliferation which become reflected in the cells appearing in the peripheral blood.

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.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 290-290 ◽  
Author(s):  
Esperanza Such ◽  
Leonor Senent ◽  
Benet Nomdedeu ◽  
Javier Bueno ◽  
Teresa Bernal ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Who Classification ◽  
Multivariate Analyses ◽  
Lower Proportion ◽  
Chronic Myelomonocytic Leukemia ◽  
Refractory Anemia ◽  
Monocyte Count ◽  
Ring Sideroblasts ◽  
Myelomonocytic Leukemia

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.

Dandelion Root and Chronic Myelomonocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5216-5216 ◽  
Author(s):  
Caroline Hamm ◽  
Sindu M. Kanjeekal ◽  
Rasna Gupta ◽  
Wendy Ng
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Hematological Malignancies ◽  
Chronic Myelomonocytic Leukemia ◽  
High Dose ◽  
Root Extract ◽  
Monocytic Leukemia ◽  
Myelomonocytic Leukemia ◽  
Acute Myeloid

Abstract Case 1 70 year old man presented with acute myelo-monocytic leukemia diagnosed in June 2009. He demonstrated no response to standard 7+3, nor high dose AraC. He remains in remission from his acute leukemia 4 years from his diagnosis, as long has he remains on the dandelion root tea, which was started immediately after chemotherapy. If he takes less than three cups / day of the DRT, his peripheral blood monocytes start to rise.1 Repeat testing demonstrates chronic myelomonocytic leukemia. Case 2 Sixty year old female with acute myelomonoctyic leukemia possibly progressing from chronic myelomonocytic leukemia. She underwent induction chemotherapy with 7+3. Her day 28 marrow showed no evidence of remission. She then underwent re-induction with high dose Ara-C at 3 gm/ m2 x 6 doses. She did receive neupogen support, and on day 28, her peripheral blood white blood count was 60 x 109/L with monocytes of 3.0 x 109/L and blasts 1.2 x 109/L. Repeat bone marrow biopsy identified chronic myelomonocytic leukemia (CMML). She stopped the neupogen and started dandelion root tea, three cups per day. She is now 5 months from her initial diagnosis and remains in complete hematological response: WBC 4.2/ Hgb 127 / Platelet 182/ Neutophils 2.6 / Monocytes 0.8. Other Cases We have had other possible cases that may support the efficacy of this product in refractory hematological malignancies. In one case of CMML-2 a 76 year old man did receive azacytadine for the duration of his treatment, as well as DRT. He finally succumbed to his disease at 30 months after his diagnosis. We previously presented an elderly female that used only DRT to treat her CMML and experienced a hematological remission for 3 months prior to relapse. Her initial WBC was 130,000 x 109/L.3 Another case of acute myeloid leukemia, who, because of co-morbidities was not a candidate for more aggressive options, relapsed from her M2- acute myeloid leukemia in November 2010. She was treated with low dose AraC, and then dandelion root tea. Although she remained transfusion dependent, she only developed peripheral blasts when she was unable to find the DRT for one month. She continues on the DRT at 15 month from relapse of her acute leukemia.3 We have a phase 1 clinical trial open at our centre investigating a novel formulation of dandelion root extract in refractory hematological malignancies. We plan to study the molecular pathways previously described in CMML including TET2 , CBL , NRAS, KRAS, JAK2 and RUNX1. http://www.ontario.canadiancancertrials.ca/trial/Default.aspx?dsEndecaNav=Ro%3A0%2CNs%3AP_TrialStatus_sort_en%7C101%7C-1%7C%2CNrc%3Aid-30-dynrank-disabled%7Cid-130-dynrank-disabled%7Cid-131-dynrank-disabled%7Cid-132-dynrank-disabled%7Cid-619-dynrank-disabled%7Cid-620-dynrank-disabled%7Cid-621-dynrank-disabled%7Cid-622-dynrank-disabled%7Cid-4294965875-dynrank-disabled%2CN%3A4294952782&TrialId=OCT1226&lang=en 1 Caroline Hamm and Sindu M. Kanjeekal, Unusual Response of Acute Monocytic Leukemia to Dandelion Root Extract, Blood (ASH Annual Meeting Abstracts), Nov 2011; 118: 4288 2. Kohlmann A, Grossmann V, et al. Next Generation Sequencing of Technology Reveals a Characteristic Pattern of Molecular Mutations in 72.8% of Chronic Myelomonocytic Leukemia by Detecting Frequent alterations in TET2, CBL, RAS, and RUNX1. JCO (28) 2009. 3. Ng W, Hamm C. Can Dandelions Cure? Schulich School of Medicine Research Day, 2009 Disclosures: No relevant conflicts of interest to declare.

scholarly journals Systemic mastocytosis with chronic myelomonocytic leukemia followed by transformation into acute myeloid leukemia

2020 ◽  
Vol 51 (1) ◽  
pp. 51-55
Author(s):  
Marta Panz-Klapuch ◽  
Krzysztof Woźniczka ◽  
Anna Koclęga ◽  
Anna Kopińska ◽  
Kinga Boral ◽  
...  
Keyword(s):  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Lymph Node Biopsy ◽  
Blood Film ◽  
Chronic Myelomonocytic Leukemia ◽  
Acute Monocytic Leukemia ◽  
Trephine Biopsy ◽  
Monocytic Leukemia ◽  
Myelomonocytic Leukemia ◽  
Abdominal Lymphadenopathy

AbstractIntroductionSystemic mastocytosis (SM) with an associated hematological neoplasm (SM-AHN) constitutes about 40% of all patients with SM. AHN commonly includes myeloid neoplasms and chronic myelomonocytic leukemia (CMML) is seen in about 30% of these patients.Case reportA 67-year-old male presented to hematologist with fatigue and significant weight loss. Abdominal ultrasound and computed tomography (CT) detected hepatosplenomegaly, abdominal lymphadenopathy, and ascites. He was anemic with leukocytosis and eosinophilia. Trephine biopsy showed > 30% of spindle-shaped mast cells. The KITD816V mutation was present. Serum tryptase level was elevated to 62 ng/mL. The patient was diagnosed with aggressive SM and received six cycles of cladribine with partial response. Three years later, he developed severe anemia. Eosinophilia and monocytosis (5.6 × 109/L) were demonstrated in blood film. Hepatosplenomegaly and abdominal lymphadenopathy were also present. Trephine biopsy did not demonstrate the presence of spindle-shaped mast cells, but dysplasia in erythroid and myeloid lineages was evident. The histological result of lymph node biopsy as well as blood and bone marrow findings were in line with CMML. He received hydroxyurea, but he transformed soon into fatal acute monocytic leukemia.ConclusionsThe prognosis of SM-AHN depends on AHN component. Leukemic transformation of AHN component may occur in a proportion of patients.

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

Blood ◽  
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.

scholarly journals Chronic Myelomonocytic Leukemia in Qatar, Single Institute Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-38
Author(s):  
Samah Kohla ◽  
Sarah Elkourashy ◽  
Feryal Abbas ◽  
Susanna Jane Akiki ◽  
Mohamed A Yassin
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Young Adults ◽  
High Risk ◽  
Chronic Myelomonocytic Leukemia ◽  
Active Management ◽  
World Health ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Myelomonocytic Leukemia

Background Chronic myelomonocytic leukemia (CMML) is a rare de novo clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). The diagnosis is challenging and carrying risk for leukemic transformation. The median age at CMML diagnosis is ~71-73 years, with a male preponderance. According to the 2016 World Health Organization (WHO) classification of myeloid neoplasms, CMML is characterized by the presence of sustained (&gt;3 months) peripheral blood (PB) monocytosis (≥1 × 109/L; monocytes ≥10% of white blood cell count) along with dysplastic features in the bone marrow (BM). &lt; 20% blasts/blasts equivalent in the PB and BM. It has recommended categorization of CMML into "proliferative" (MPN-CMML) and "dysplastic" (MDS-CMML) sub-types; based on a total leukocytic count (TLC) (of ≥13 × 109/L for MPN-CMML). Also, based on PB and BM blast %, CMML can be sub-classified into three categories; (a) CMML-0 (&lt;2% PB blasts including promonocytes and &lt;5% BM blasts), (b) CMML-1 (2-4% PB blasts including promonocytes and 5%-9% BM blasts), and (c) CMML-2 (&gt;5% PB blasts including promonocytes and 10%-19% BM blasts and/or when any Auer rods are present. Objective: To retrospectively analyze the cases of CMML diagnosed in the Hematology Department, National Center for Cancer Care and Research (NCCCR), Doha, Qatar from January 2013 to July 2020 with the assessment of risk and prognosis. Materials and methods: The results from flow cytometry, cytology, PB, and BM morphology, cytogenetics and molecular genetics were re-estimated. The CMML-specific prognostic scoring system (CPSS) was used for the risk stratification. Results:12 patients diagnosed as CMML were detected and included in the study, 10 males and 2 females, with a median age of 64 years. 3 Arabs and 9 non-Arabs. 10 patients were transfusion dependent. 6 patients had splenomegaly and 2 of them had massive splenomegaly (&gt;20 cm in craniocaudal length). According to the TLC, 8 were myeloproliferative (CMML/MP) and 4 were myelodysplastic CMML. 4 of our patients were below 40 years (classified as young adults as per WHO) and all were of the proliferative type. The flow cytometry of PB and/or BM was done to 11 patients. The monocytic cells were characterized by co-expressing CD14 and CD64 and showed aberrant expression of CD56 on 5 patients. According to the morphology of the BM, one case was described as MDS/MPN or MPN, and the rest of the cases were diagnosed as MDS/MPN. According to WHO 2016 diagnostic criteria of CMML: one case was diagnosed as CMML0, one case was diagnosed as CMML1, 9 cases were diagnosed as CMML2 and one case was diagnosed as MPN/MDS -CMML2 or as MPN. The cytogenetic risk was high in 4 patients, intermediate in one patient, and low in 7 patients. According to CPSS, one patient was an intermediate risk I, 4 was intermediate-risk II, and 7 were high risk. Molecular analysis and NGS were done for 4 patients that were most recently diagnosed. One case showed NRAS in 30%, one case showed KRAS in 57%, one case showed DNMT3A and NPM1 each 42% and one case showed WT1 (36%), FLT3 (33%) and NPM1 (15%). Regarding management and supportive care, 10 out of 12 patients required transfusion support. 4 patients (3 Proliferative and one Dysplastic) were not eligible for active management and received only symptomatic treatment. 5 patients of the proliferative type were started on hydroxyurea. The other 3 patients were of dysplastic subtype who received hypomethylating agent +/- allogenic bone marrow transplant. 6 patients traveled back to their home country and lost follow up, 5 expired, and one patient still alive. Conclusion: CMML is a unique and rare hematopoietic neoplasm with complex biology and pathology. It is an aggressive rare disease that carries a dismal prognosis, with poor survival and a high risk of transformation. The therapeutic options are limited. In our clinic, for the 7 years period, CMML was confirmed only in 12 patients. The great majority of them were old males of the non-Arab nationality, transfusion-dependent, presented with TLC (&gt; 13x10^3/ul Proliferative) of CMML2 subtype and high CPSS risk score. 33% of our patients were young adults (less than 40 years old) and were of the proliferative type. The combination of clinical, morphological, immunophenotyping, cytogenetic and molecular information is required to improve the accuracy of CMML prognostication. Disclosures No relevant conflicts of interest to declare.

scholarly journals Diagnostic Utility of Flow Cytometric Immunophenotyping in Chronic Myelomonocytic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5526-5526
Author(s):  
Leonor Arenillas ◽  
Ivonne Parraga ◽  
Lourdes Florensa ◽  
Sara Montesdeoca Romero ◽  
Anna Puiggros ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Chronic Myelomonocytic Leukemia ◽  
Nonspecific Esterase ◽  
Age Related ◽  
Hla Dr ◽  
Myelomonocytic Leukemia ◽  
Classical Monocytes

Abstract INTRODUCTION The diagnosis of chronic myelomonocytic leukemia (CMML) according to WHO 2017 requires the presence of ≥1x109/L and ≥10% of monocytes in peripheral blood (PB). Establish an accurate diagnostic is difficult since many clinical situations present persistent monocytosis. The presence of dysplasia, mainly dysgranulopoiesis, is frequent but not always present in CMML. Cytogenetic aberrations are infrequent in this disease (20-25% of cases). Although 85-90% of CMML patients present at least one mutation in TET2, SRSF2 or ASXL1 genes, the use of NGS panels is not widespread. Furthermore, mutations in these genes are among the most frequently observed in age-related clonal hematopoiesis. Therefore, complementary techniques are required to support the diagnosis of this entity. The study of the peripheral monocyte subsets by flow cytometry (FC) has gained special interest due to a high sensitivity and specificity for the diagnosis of CMML (S = 90.6%, E = 95.1%, Selimoglu-Buet et al., Blood, 2015). An increase in the fraction of classical monocytes (Mo1) to >94% of total monocytes is an event frequently observed in CMML. There are no specific bone marrow (BM) FC panels for the diagnosis of CMML and very few have been validated for the diagnosis of MDS. "Ogata score", the only multicenter validated score in MDS, has not been applied in CMML. The aim of our study was to evaluate the usefulness of FC in PB and BM for the diagnosis of CMML. METHODS Twenty-two CMML were prospectively studied from 02/2016 to 04/2018. Patients' characteristics are summarized in Table 1. Diagnostic procedure consisted of morphological, cytochemical (Perls, myeloperoxidase, nonspecific esterase), cytogenetic and FC studies in BM, and morphological and FC studies in PB. "Ogata Score" was applied in BM samples (Table 2). Aberrant coexpression of CD2, CD7 and CD56 in BM monocytes was assessed. Immunophenotypic maturation profile of the monocytic elements in BM distinguishes: promonocytes (CD34-/CD117-/CD64++/CD14- or dim/CD45+/HLA-DR+++), mature monocytes (CD34-/CD117-/CD64++/CD14++/CD45++/HLA-DR++) and mature monocytes in terminal stage (CD300e+). In PB, the monocytes FC subsets (Mo1, Mo2 and Mo3) were studied, as well as the aberrant coexpression of CD2, CD7 and CD56 (Table 3). RESULTSThe presence of ≥2 aberrations in Ogata Score predicted properly the diagnosis of CMML in all patients analyzed (100% sensitivity). Due to the study design, we could not obtain results about specificity.An increase in Mo1 (classical monocytes) > 94% was detected in 18/20 patients (Table 3). This method predicted the diagnosis of CMML with a sensitivity of 91%, a result almost identical to the original study (Selimoglu-Buet et al., Blood, 2015).A good positive correlation was established between the percentage of BM promonocytes detected by morphology and by FC (Rho Spearman 0.61, P = 0.003).A negative correlation was found between the percentage of promonocytes by FC in MO and the expression of CD56 (Rho Spearman -0.612, P = 0.002). Similarly, CD56+ CMML presented a percentage of promonocytes by FC significantly lower than the CD56- CMML group (median: 24.5% (14-40) vs. 41% (23-71), P = 0.005). The expression of CD56 seems to be related to a more mature immunophenotypic profile of the monocytic population. On the other hand, the correlation between the percentage of CD56+ monocytes in BM and PB was almost perfect (Rho Spearman 0.928, P <0.001). CONCLUSION Our findings support the usefulness of flow cytometry in bone marrow and peripheral blood for the diagnosis of CMML. Disclosures No relevant conflicts of interest to declare.

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