ISSN: ISSN: 2329-8790
Monosomy 7 is a frequent karyotypic abnormality in de novo or therapy-related MDS (t-MDS). The overall prognosis of patient with monosomy 7 remains poor. However, a small number of case reports from pediatric literature describe spontaneous resolution of Myelodysplastic Syndrome (MDS) with monosomy 7. Herein we document first report of spontaneous remission of t-MDS with monosomy 7 in an adult patient.
Monosomy 7; Myelodysplastic syndrome; Breast cancer
A 58-year-old female from the West Indies developed right T2N2AM0, stage IIIA breast cancer in August 2014 [1-3] that was HER-2neu and ER/PR positive. She completed pegfilgrastim supported neoadjuvant chemotherapy (pertuzumab 840 mg IV × 1 then 420 mg IV, trastuzumab 4 mg/kg × 1 then 2 mg/kg, Docetaxel 75 mg/m2 and carboplatin with AUC-6 every 3 weeks × 6 cycles) in January 2015. A right breast lumpectomy in February 2015 revealed residual disease (4 mm) and she underwent external Beam Radiation (XRT) to the right breast in May 2015. She completed adjuvant herceptin in September 2015. All chemotherapies were administered without dose delay or dose reduction . While on adjuvant letrozole, at the tail end of herceptin therapy, she presented in August 2015 with fatigue and pancytopenia (Table 1). In September 2015, she required 2 units of packed red cell transfusion for hemoglobin of 5.9 gm/dL and hematocrit of 17.6%. Her cytopenia progressed to white cell count of 1.2 (absolute neutrophil count 400) and platelets of 43,000. A repeat Complete Blood Count (CBC) following week revealed White Cell Count (WBC) of 1.46 (absolute neutrophil count 800), hemoglobin 9.3 and platelets of 81,000. Blood tests for B12, folate deficiency, hemolysis, iron deficiency and Paroxysmal Nocturnal Hemoglobinuria (PNH) profile was negative CT scan of abdomen did not reveal splenomegaly  for the continued pancytopenia of 3 months duration, she underwent a bone marrow biopsy in October 2015 that revealed monosomy 7 and myelodysplastic changes in hypercellular marrow (85%) showing dysplastic changes in the erythroid and megakaryocytic lines and 2% blasts. Cytogenetic analysis revealed monosomy 7 in 7 cells of 20 cells examined (35% cells) and Fluorescent in-situ Hybridization (FISH) analysis showed deletion of 7q in 50% of the cells analyzed. Table 1 show to illustrate serial blood counts, cytogenetics and bone marrow morphology. Diagnosis of intermediate risk MDS (R-IPSS score- 4.5) necessitated a consultation for allogeneic hematopoietic transplantation. However, after 4 months of persistent pancytopenia, she began to recover blood counts with resolution of both cytopenia and monosomy 7 Morphologic improvement in MDS preceded cytogenetic improvement [6,7] (Table 1).
|Oct-15||1.46||800||9.3||81||MDS||Monosomy 7 in 35% cells|
|May-16||8.2||7000||11.8||242||No MDS||Monosomy 7 in 5% cells|
|Dec-16||6.1||4400||11.3||268||No MDS||Monosomy 7 in 0% cells|
|Note: WBC=White Blood Count (x109/L), ANC=absolute neutrophil counts, Hb=hemoglobin (gm/dL), Platelets (x109/L);BM= Bone Marrow Morphology.|
Table 1: Cytopenia, marrow dysplasia and monosomy 7 following completion of cytotoxic chemotherapy in January 2015.
Such spontaneous resolution of monosomy 7 has not been previously reported in adults . So far the 2 oldest patients reported are 19 years old [4-6] those reported from pediatric population is summarized in the overall incidence of MDS/AML in breast cancer patients following treatment with chemotherapy and radiation therapy is approximately 0.29%. The median time to develop MDS/AML was 3.06 years (Range=0.41-12.95 years) . Furthermore, granulocyte colony-stimulating factor (G-CSF) administration has been linked to the development of monosomy 7 in severe congenital neutropenia and aplastic anemia . It has been suggested that pharmacologic doses of G-CSF increase the proportion of preexisting monosomy 7 cells. The abnormal response of monosomy 7 cells to GCSF can be explained by the expansion of undifferentiated monosomy 7 clones expressing the class IV GCSFR, which is defective in signaling cell maturation  (Table 2).
|Author||Patients||Age/Sex||MDS type||CR duration|
|Mamtadakis 1999||4||8 months, male||t-MDS||108 months|
|Parker 2008||1||15 months, male||t-MDS||14 months|
|Renneboog 1996||1||8 years, male||t-MDS||67 months|
|Scheurlen 1994||1||10 years, male||t-MDS||95 months|
|Laver 1997||2||3 years, male||t-MDS||30 months|
|De novo||2||19 years, male||t-MDS||12 months|
|Yang 2017||1||14 months, male||t-MDS||4 months|
Table 2: Reported monosomy 7 associated spontaneous MDS remission.
It remains unclear whether our patient developed monosomy 7 clone secondary to chemotherapy or G-CSF or she had a preexisting clone. From the reported pediatric literature several hypotheses have emerged to explain transient abnormal hematopoiesis. It is postulated that aberrant clone may be unable to maintain its proliferative advantage as clonal loss of one copy of a critical 7q tumor suppressor gene may ultimately regress in absence of a “second hit”. Another proposed hypothesis is self-limiting clonal aberration because it did not develop from stem cell pool . Yet another plausible explanation is extrapolated from patients with severe aplastic anemia who develop MDS in context of immunosuppressive therapy [9,10]. Recovery of immune effector function following completion of chemotherapy may account for disappearance of malignant clone.
This report highlights importance of recognition and stringent follow-up without therapeutic intervention in select t-MDS.
Citation: Kamble R, Mukherjee A, Shagufta N, Scholoff A, Gloria O, Carrum G. (2019) Spontaneous Resolution of Monosomy and Treatment Related Myelodysplastic Syndrome in a Breast Cancer Survivor J Hematol Thrombo Dis 2019, 7:298.
Received Date: Nov 14, 2018 / Accepted Date: Dec 26, 2018 / Published Date: Jan 04, 2019
Copyright: © 2019 Kamble R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.