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LETTERS TO EDITOR  
Year : 2020  |  Volume : 63  |  Issue : 2  |  Page : 339-341
A rare case of therapy-associated acute megakaryoblastic leukemia


1 Department of Hematopathology, Manipal Hospital, Bengaluru, Karnataka, India
2 Department of Medical Oncology, Manipal Hospital, Bengaluru, Karnataka, India

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Date of Web Publication18-Apr-2020
 

How to cite this article:
Shekhar R, Rauthan A, Pai S. A rare case of therapy-associated acute megakaryoblastic leukemia. Indian J Pathol Microbiol 2020;63:339-41

How to cite this URL:
Shekhar R, Rauthan A, Pai S. A rare case of therapy-associated acute megakaryoblastic leukemia. Indian J Pathol Microbiol [serial online] 2020 [cited 2020 May 31];63:339-41. Available from: http://www.ijpmonline.org/text.asp?2020/63/2/339/282702




Dear Editor,

The 2008 WHO classification defined therapy-related myeloid neoplasms (t-MNs) as those cases of acute myeloid leukaemia (AML), myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) that develop as a late complication of cytotoxic chemotherapy or radiation therapy given for a prior condition.[1] They account for 10-20% of all cases of AML, MDS and MDS/MPN. Acute megakaryoblastic leukemia accounts for <5% of all cases of acute myeloid leukemia (AML). To the best of our knowledge till date there have been no reports of therapy-related acute megakaryocytic leukaemia in India. We present a rare case of a patient of ovarian carcinoma who developed therapy related acute megakaryocytic leukemia 2.5 years after administration of chemotherapy.

A 45 year old woman was diagnosed with ovarian carcinoma (stage IIIc) in March 2015. The patient received six cycles of chemotherapy with paclitaxel and carboplatin and cytoreductive surgery.

In March 2016 she developed rising CA-125 levels. CT scan of her abdomen and pelvis revealed extensive disease in the abdomen with multiple peritoneal secondaries. Histopathological examination showed recurrent carcinoma ovary. The intraperitoneal cisplatin and six cycles of carboplatin and liposomal doxorubicin. She also received next line chemotherapy with gemcitabine and carboplatin.

The patient repeatedly presented with complaints of leg pain along with anemia and thrombocytopenia. She was treated with multiple platelet and packed RBC transfusions but the low counts persisted. In September 2017, in view of the persistent cytopenias, a bone marrow aspiration and biopsy were done. Bone marrow aspirate was extremely dilute and hypocellular. The biopsy only revealed small areas of cellularity. Immunohistochemistry for cytokeratin did not highlight epithelial cells. A repeat biopsy and aspirate was advised. PET-CT performed at this time revealed reduction in disease in the abdomen and peritoneum.

The patient's total WBC count remained low to normal with anemia and thrombocytopenia until the end of January 2018 when the patient was readmitted with complaints of severe cough, anemia, low platelet counts, high total count, and fever. Her hemoglobin was 5.8 gm%, platelet count was 44,000/cu.mm, and total WBC count was 23,100/cu.mm. She was given PRBC and SDP transfusions and a peripheral smear was sent.

The peripheral smear revealed 64% blasts along with normocytic hypochromic anemia and thrombocytopenia. The blasts were moderate to large in size with moderate amount of basophilic cytoplasm. The cytoplasm showed blebbing/pseudopod formation and many giant platelets were seen in the smear [Figure 1]a and [Figure 1]b: Moderate sized blasts with basophilic cytoplasm and blebbing/pseudopod formation. Giant platelets were also seen (Leishman stain x1000)].
Figure 1: (a and b): Moderate-size blasts with basophilic cytoplasm and blebbing/pseudopod formation. Giant platelets were also seen (Leishman stain x1000)

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Flow cytometry was done on the peripheral smear. The blasts showed moderate CD34 (subset), bright CD36, moderate CD71 and CD38, dim CD33 and CD117 with negative CD13, HLADR, CD235a and MPO. Aberrant moderate (subset) positivity for CD7 was seen. CyCD41a and CyCD61 were positive and a diagnosis of therapy-related acute megakaryoblastic leukemia (M7) was made.

The WHO broadly recognizes two clinical subsets of therapy-related myeloproliferative neoplasms. The first and the most common type occurs 5–10 years after exposure to alkylating agents and/or ionizing radiation. These patients often present with MDS and bone marrow failure.

The second subset occurs earlier (within 1–5 years) following treatment with agents that interact with DNA topoisomerase II. Many of these patients present as an overt leukemia without a myelodysplastic phase.

Our patient may have had a possible myelodysplastic phase between September 2017 and January 2018 as she had cytopenias during this time. However, she presented with an overt leukaemia within 3 years of starting chemotherapy. It is therefore likely that her t-AMKL was induced by a topoisomerase II inihibitor (doxorubicin) although she was also treated with an alkylating agent (carboplatin).

The blasts in AMKL express platelet glycoproteins (CD41 and CD61) while CD34, CD45, anti-MPO and HLA-DR are negative. Our patient showed a similar immunophenotype along with CD36 and aberrant CD7 expression.

AMKL is most common in children and is very rarely seen in adults (<2% of all AMLs). In children, AMKL has shown a strong association with patients with Down syndrome while t(1;22) is seen in those pediatric cases which do not have Down syndrome. In adults, the chromosomal abnormalities are more diverse including aberrations of chromosomes 3, 5 and 7.[2],[3] Unfortunately, due to financial constraints, cytogenetic studies could not be done in our patient.

An earlier study reported 4 t-AMKLs out of 37 AMKL studied while another study reported t-AMKL in 2 of 23 adult AMKL cases.[4] Studies also suggest that adult AMKL is most common after either a prior hematologic neoplasm or after chemotherapy for a neoplastic disorder.[5]

AMKL is a rare leukemia in adults and to the best of our knowledge this is the first reported case from India of therapy-associated acute megakaryoblastic leukemia.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised. 4th ed. Lyon: IARC; 2017. p. 153-5.  Back to cited text no. 1
    
2.
Pagano L, Pulsoni A, Vignetti M, Mele L, Fianchi L, Petti MC, et al. Acute megakaryoblastic leukemia: Experience of GIMEMA trials. Leukemia 2002;16:1622-6.  Back to cited text no. 2
    
3.
Tallman M, Neuberg D, Bennett J, Francois C, Paietta E, Wiernik P, et al. Acute megakaryocytic leukemia: The eastern cooperative oncology group experience. Blood 2000;96:2405-11.  Back to cited text no. 3
    
4.
Duchayne E, Fenneteau O, Pages MP, Sainty D, Arnoulet C, Dastugue N, et al. Acute megakaryoblastic leukaemia: A national clinical and biological study of 53 adult and childhood cases by the Groupe Francais d'Hematologie Cellulaire (GFHC). Leuk Lymphoma 2003;44:49-58.  Back to cited text no. 4
    
5.
Oki Y, Kantarjian H, Zhou X, Cortes J, Faderl S, Verstovsek S, et al. Adult acute megakaryocytic leukemia: An analysis of 37 patients treated at M.D. Anderson cancer center. Blood 2006;107:880-4.  Back to cited text no. 5
    

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Correspondence Address:
Swati Pai
Manipal Hospitals, 98, HAL Old Airport Road, Kodihalli, Bengaluru - 560 017, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_579_18S

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