Acute monoblastic/monocytic leukemia and chronic myelomonocytic leukemia share common immunophenotypic features but differ in the extent of aberrantly expressed antigens and amount of granulocytic cells

2011 ◽  
Vol 52 (1) ◽  
pp. 92-100 ◽  
Author(s):  
Wolfgang Kern ◽  
Ulrike Bacher ◽  
Claudia Haferlach ◽  
Susanne Schnittger ◽  
Torsten Haferlach
Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5216-5216 ◽  
Author(s):  
Caroline Hamm ◽  
Sindu M. Kanjeekal ◽  
Rasna Gupta ◽  
Wendy Ng

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.


2020 ◽  
Vol 51 (1) ◽  
pp. 51-55
Author(s):  
Marta Panz-Klapuch ◽  
Krzysztof Woźniczka ◽  
Anna Koclęga ◽  
Anna Kopińska ◽  
Kinga Boral ◽  
...  

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.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3799-3799
Author(s):  
Wolfgang Kern ◽  
Claudia Haferlach ◽  
Susanne Schnittger ◽  
Torsten Haferlach

Abstract 3799 Poster Board III-735 Acute monoblastic/monocytic leukemia (AMoL) is grouped into acute myeloid leukemia and related neoplasms by the 2008 WHO classification while chronic myelomonocytic leukemia (CMML) in grouped into myelodysplastic/myeloproliferative neoplasms (MDS/MPN). However, both entities share common features and sometimes may be difficult to differentiate from each other. In particular, monopoietic cells can be easily identified by multiparameter flow cytometry (MFC) based on their CD45/side-scatter (SSC) signal. However, immunophenotypes of monoblasts and dysplastic monocytes largely overlap. Their differentiation from each other is better accomplished by cytomorphology (CM) and the use of non-specific esterase. We compared cytomorphologic, immunophenotypic and cytogenetic results between 26 patients with AMoL and 139 patients with CMML which were analyzed at diagnosis between 2005 and 2009 in order to identify shared and discriminative characteristics. In AMoL vs. CMML 65.4% vs. 73.4% were male, the median age was 65.4 vs. 72.5 years (range 19.3-82.0 vs. 21.9-87.9 years, p<0.001), and the median WBC count was 38.0 G/L vs. 10.4 G/l (range 0.8-126.0 G/l vs. 0.9-92.0 G/l, p<0.001). Cytogenetics differed in that a normal karyotype was found in 79.1% of CMML cases and in only 38.5% of AMoL cases (p<0.0001). Per definition, a t(9;11) (19.2%) was found only in AMoL (p<0.001) which was almost identical for other translocations involving MLL (15.4% vs. 0.7%, p=0.003). Other cytogenetic abnormalities did not significantly differ between AMoL and CMML. First, immunophenotypes of monopoietic cells were compared between AMoL and CMML. While an aberrant coexpression of CD56 was present in all cases with AMoL this was true in only 82.0% of CMML cases (p=0.015). No other aberrantly expressed antigen was found in AMoL while in CMML a coexpression of CD2 was found in 21.6% (p=0.005), a lack of CD13 expression in 10.8% (n.s.), and a lack of HLA-DR expression in 4.3% (n.s.). Next, we compared the frequencies of different cell types between AMoL and CMML as identified by CM and MFC. In this analysis, granulocytic cells by CM included cells of all maturation grades from promyelocyte to granulocyte, which corresponds to the population identified in MFC by their dim expression of CD45 and their strong SSC signal. As anticipated when considering the definition of the respective entities CM identified higher percentages of blasts (mean±SD 78.7±13.8 vs. 8.6±5.1, p<0.001) and lower percentages of monocytes (1.7±3.9 vs. 13.8±11.9, p<0.001) and granulocytic cells (7.9±7.4 vs. 53.8±15.8, p<0.001) in AMoL vs. CMML. Applying the blast gate in the CD45/side-scatter analysis for the identification of blasts (CD45(+)SSC-) MFC also found higher percentages of blasts in AMoL vs. CMML (18.2±25.1 vs. 4.0±3.2, p<0.001) and monopoietic cells were found also at higher frequencies in AMoL (28.6±27.4 vs. 20.1±12.3, p=0.012). Interestingly, however, MFC identified significantly higher frequencies of granulocytic cells in CMML (52.2±19.3 vs. 26.2±22.6, p<0.001). Thus, while the CD45-SSC analysis is not capable of differentiating between monocytes and monoblasts it may be used to identify high percentages of granulocytic cells which is characteristic for CMML but not for AMoL. Based on these findings, the ratio M:G (monopoietic cells:granulocytic cells) was calculated for each case. The ratio M:G was significantly higher in AMoL as compared to CMML (mean±SD 5.2±10.4 vs. 0.8±2.3, p<0.001). In conclusion, the present data demonstrate that AMoL and CMML after being discriminated according to WHO guidelines for cytomorphology share common features as identified by MFC but differ in the extend of aberrantly expressed antigens and the amount of granulocytic cells. For further studies and to support CM these parameters should be evaluated when using MFC as a diagnostic tool for AMoL and CMML. Disclosures: Kern: MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.


Morphologia ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 49-57
Author(s):  
L. A. Pesotskaya ◽  
A. S. Korolenko

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).


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4288-4288
Author(s):  
Caroline Hamm ◽  
Sindu M. Kanjeekal

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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