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Year : 2011  |  Volume : 54  |  Issue : 2  |  Page : 371-373
Therapy related myelodysplastic syndrome: A case report and review of literature

Department of Pathology, LTMG Hospital, Sion, Mumbai, India

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Date of Web Publication27-May-2011


Therapy related myeloid neoplasm is directly related to previous cytotoxic chemotherapy or radiation therapy. We present a 47-year-old lady who developed therapy related myelodysplastic syndrome (MDS) 2.5 years after she received four cycles of chemotherapy and local radiation therapy for carcinoma breast. She presented with bicytopenia with trilineage dyspoiesis in the peripheral blood, bone marrow aspirate and biopsy. Fluorescent in-situ hybridization studies did not reveal any of the common abnormalities associated with MDS. A diagnosis of therapy related MDS was rendered. Different studies have shown that patients treated with alkylating agents and ionizing radiation present as MDS with a latent period of 3-10 years. Our patient developed MDS within 2.5 years of starting chemotherapy and radiotherapy and did not reveal any of the conventional cytogenetic abnormalities. It highlights the importance of simple tests like a complete blood count and peripheral blood smear examination in follow-up of the patients treated with chemotherapy.

Keywords: Alkylating agents, myelodysplastic syndrome, therapy related, topoisomerase inhibitors

How to cite this article:
Sonawane S, Gadgil N, Margam S. Therapy related myelodysplastic syndrome: A case report and review of literature. Indian J Pathol Microbiol 2011;54:371-3

How to cite this URL:
Sonawane S, Gadgil N, Margam S. Therapy related myelodysplastic syndrome: A case report and review of literature. Indian J Pathol Microbiol [serial online] 2011 [cited 2021 Jun 13];54:371-3. Available from: https://www.ijpmonline.org/text.asp?2011/54/2/371/81643

   Introduction Top

Therapy related myeloid neoplasm is a heterogeneous group of clonal hematopoietic stem cell disorders and is directly related to previous cytotoxic chemotherapy or radiation therapy. It includes myelodysplastic syndrome (MDS), acute myeloid leukemia, myelodysplastic/myeloproliferative neoplasm. [1],[2],[3],[4]

   Case Report Top

A 47-year-old lady presented in April 2010 with complaints of weakness and giddiness of 1 month duration. Her hemoglobin (Hb) was 3.9 g/dl, white blood cell (WBC) count 16,500/mm 3 and platelet count 43,000/mm 3 . Peripheral blood smear showed immature myeloid precursors (including hypogranular myeloid cells and pseudo-pelger huet cells) and 4% blasts.  Auer rods More Details were seen [Figure 1], [Figure 2] and [Figure 3]. Bone marrow aspiration revealed 6% blasts with trilineage dyspoiesis. Apart from dyspoietic myeloid and erythroid precursors, micromegakaryocytes and monolobated megakaryocytes were seen. Bone marrow biopsy was hypercellular and showed trilineage dypoiesis [Figure 4]. Reticulin stain revealed mild degree of paratrabecular fibrosis. Stains for CD34 did not highlight any increase in blast percentage. Flow cytometric immunophenotyping revealed myeloid nature on scanty blasts samples (blasts expressed CD13, CD33 and CD117). Fluorescent in-situ hybridization (FISH) studies did not reveal any of the common abnormalities associated with MDS. There was no evidence of del7q del9q, MLL translocation, t(5:12), PDGRF-B rearrangement, BCR-abl gene rearrangement or Jak2, v617F mutations.
Figure 1: Peripheral blood smear showing a blast with an Auer rod in the cytoplasm (Wright Stain, oil immersion)

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Figure 2: Peripheral blood smear showing dyserythropoietic cells showing cytoplasmic to cytoplasmic bridging (Wright Stain × oil immersion)

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Figure 3: Peripheral blood smear showing bilobed neutrophils (pseudo-pelger huet cells) (Wright Stain × oil immersion)

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Figure 4: Hypercellular packed bone marrow biopsy showing dysmegakaryopoiesis (H and E, ×10)

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Past history revealed that she had left breast lumpectomy for Infiltrating Lobular Carcinoma (ILC) in August 2007. Tumor cells expressed estrogen and progesterone receptors, while cerbB2 was negative. Hemogram was unremarkable at that time, which revealed Hb of 12.1 g/d1, WBC count 11,000/mm 3 and platelet count 272,000/mm 3 . She received four cycles of CEF protocol (cyclophosphamide, epirubicin and 5-flurouracil) over a period of 4 months, along with four cycles of paclitaxel. This was followed by local radiotherapy (15 Gy in 25 fractions) over 5 weeks. She continued to receive oral tamoxifen. She was diagnosed as a therapy related MDS, refractory anemia with excess blasts and was put on supportive therapy. However, she expired 5 months after the diagnosis was made.

   Discussion Top

Therapy related MDS has been reported after treatment of several tumors as Hodgkin's Lymphoma, non-Hodgkin's lymphoma, various sarcomas, and carcinoma of testis, ovary and breast. [1] Proportion of patients developing therapy related MDS with prior hematological malignancy or prior solid tumor is similar. [2]

Therapy related MDS is uncommon and accounts for 10-20% of all cases of AML, MDS and MDS/myeloproliferative neoplasm (MPN). [3] Cumulative incidence of therapy related MDS or AML is 2% at 15 years after conventional therapy with alkylating agents. [1] Other studies have revealed that MDS develops after a latent period of 5-10 years [1] and after 3-5 years. [5]

Therapy related MDS is commonly associated with chemotherapeutic drugs (alkylating agent and topoisomerase II inhibitors) and with radiotherapy. Amongst the alkylating agents, common drugs include cyclophosphamide, isofamide, mechlorethamine, melphalan, busulfan, nitrosoureas, chlorambucil and dacarbazine. [6] Our patient received both chemotherapy (cyclophosphamide, epirubicin and 5-flouroracil) as well as radiotherapy.

Incidence amongst the patients treated with cytotoxic drugs varies according to the underlying disease specific agents, timing at exposure and dose. [2],[4] Risk associated with alkylating agents and radiation therapy increases with age, while it remains constant across all ages with topoisomerase II inhibitors. Our patient was a middle-aged lady as against the elderly age group seen in other studies. [2],[4] Cases of therapy related myeloid neoplasm that arises following therapy with alkylating agents and ionizing radiation have relatively long latency period (3-5 years) after primary exposure. [5] Patients who are exposed to topoisomerase II inhibitors tend to present with therapy related myeloid neoplasm within 1-5 years of starting chemotherapy. [4] Most of these patients do not have an overt MDS phase and directly develop AML. [3] However, our patient developed therapy related MDS, 2.5 years after starting chemotherapy.

Specific balanced chromosomal aberrations involving chromosome bands 11q23, 21q22, inv 16, t(15,17) and t(9,22) are significantly associated with DNA topoisomerase II inhibitor. Alkylating agents are associated with uncharacteristic balanced aberration and show deletion of various parts of or loss of whole long arm chromosome 5 and chromosome 7. [7] In addition, other types of balanced aberration with chromosomal loss include deletion of various parts of short arm of chromosome 12 or chromosome 17 or loss of whole chromosome 18. [7] As with other myeloid neoplasms, cytogenetic features of therapy related myeloid neoplasm are predictive of outcome. Balanced translocations are associated with relatively better prognosis, whereas loss of entire or partial chromosome 5 and 7 is associated with particularly dismal prognosis. [6] There were no such or any other cytogenetic abnormalities in our patient.

To conclude, patients treated with alkylating agents and ionizing radiation for a solid tumor might present as MDS with a latent period of 3-10 years and have common cytogenetic abnormalities. However, our patient developed MDS within 2.5 years of starting chemotherapy and radiotherapy, and did not reveal any of the commonly described cytogenetic abnormalities. Therapy related MDS/acute myeloid leukemia (AML) is generally refractory to treatment, with a median survival of 5 months. [2],[8] Our patient expired 5 months after being diagnosed as therapy related MDS.

This report highlights the importance of a regular and close follow-up of such patients with a simple test like a hemogram and peripheral blood smear so as to check on the development of any secondary hematopoietic malignancy. Any trend or a gradual drop in hemoglobin and platelet counts or a change in white cell count should alarm the treating physician.

   References Top

1.Bhatia S, Robison LL, Oberlin O, Greenberg M, Bunin G, Fossati-Bellani F, et al. Breast cancer and other second neoplasms after childhood Hodgkin's disease. N Engl J Med 1996;334:745-51.  Back to cited text no. 1
2.Ng AK, Bernardo MV, Weller E, Backstrand K, Silver B, Marcus KC, et al. Secondary malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy. Long Term risks and risk factors. Blood 2002;100:1989-96.  Back to cited text no. 2
3.Leone W, Mek L, Pulsani A, Equitani F, Pagana L. The incidence of secondary leukemias. Haematologica 1999;84:937-4.  Back to cited text no. 3
4.World Health Organization. Classification of Tumors, Pathology and Genetics. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. Tumors of Hematopoietic and Lymphoid Tissues. Lyon, France: IARC; 2001.  Back to cited text no. 4
5.Karp JE, Adoo CB. Therapy related acute leukemia. Clinical Lab Med 2000;20:71-9.  Back to cited text no. 5
6.Van Leeuwen FE, Travis LB. Second cancers. In: VT Devita, et al., editors Cancer: principles and practice of oncology. 7 th ed. Philadelphia (PA): Lippincott, Williams, and Wilkins; 2005. p. 2575-602.  Back to cited text no. 6
7.Pederson J, Bjergaard J, Andersen MK, Andersen MI, Christiansen DH. Genetics of therapy related mylodysplasia and acute myeloid leukemia. Leukemia 2008;2:240-8.  Back to cited text no. 7
8.Michels SD, McKenna RW, Arthur DC, Brunning RD. Therapy related acute myeloid leukemia and myelodysplastc syndrome, A clinical and morphological study of 65 cases. Blood 1985;65:1364-72.  Back to cited text no. 8

Correspondence Address:
Nitin Gadgil
Department of Pathology, LTMG Hospital, Sion, Mumbai
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.81643

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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