Concurrent Acute Monoblastic Leukemia and Multiple Myeloma in a 66-Year-Old Chemotherapy-Naive Woman

Concurrent acute myeloid leukemia (AML) and multiple myeloma (MM) is rare, more so in chemotherapy-naive patients. Concurrent occurrence of these two malignancies portends poor prognosis. Although anthracycline-based AML regimen, allogeneic hematopoietic stem cell transplantation, tipifarnib and bortezomib have shown promising results in small number of patients, there is a lack of established therapy. We describe a case of concurrent AML and MM in a 66-year-old woman and review previously published literature.


Introduction
Concurrent acute myeloid leukemia (AML) and multiple myeloma (MM) is rare and presents unique therapeutic challenges. Here, we describe a case of concurrent AML and MM and review previously published literature.

Case Report
A 66-year-old woman, complaining of fatigue, loss of appetite and 25-pound weight loss for 8 weeks, was seen in the ambulatory clinic at a different institution after detection of abnormalities in blood work. Her medical history was significant for 80 pack-year smoking, chronic obstructive pulmonary disease, hypercholesterolemia, hypertension, coronary artery disease, coronary stent placement, tonsillectomy and appendectomy. The patient had a good performance status. Family history was significant for breast cancer in her mother and esophageal cancer in her father. Her medications included isosorbide mononitrate, aspirin, simvastatin, metoprolol, inhalational ipratropium, albuterol and fluticasone.
Physical examination revealed temperature of 96 °F, blood pressure of 107/73 mmHg, pulse of 98/min and respiratory rate of 16/min. The patient was calm and oriented. She had pallor but no icterus, petechiae, or any other evidence of bleeding. Lymph nodes were not palpable. There was no bony tenderness. Abdominal examination did not reveal hepatosplenomegaly or any other masses. Rest of the physical examination was also unremarkable.
A bone marrow biopsy done at the other institution revealed hypercellular bone marrow with decreased bone marrow precursor cells and infiltration with plasma cells, which were kappa restricted. Flow cytometry of the bone marrow aspirate was significant for two abnormal populations: 1) myeloid cells (27% of non-erythroid cells) with immunophenotype suggestive of monocytic differentiation; 2) plasma cells (33% of total cells) positive for monoclonal IgG, kappa-restricted, positive for CD38, CD117 and CD56 consistent with MM. The patient was referred to our institution for further management.
Peripheral blood smear at our institution showed 12% blasts with Auer rods. A repeat bone marrow biopsy showed hypercellular bone marrow (70-80%) with 50-60% blasts, decreased megakaryocytes, maturing myeloid and erythroid The patient was started on allopurinol and hydroxyurea, and the latter was subsequently stopped once chemotherapy was initiated. She was induced as an in-patient with 7-day low-dose cytarabine (100 mg/m 2 /day) and 3-day idarubicin (12 mg/m 2 /day).
Her hospitalization was complicated by Clostridium difficile diarrhea, neutropenic sepsis, and hospital acquired pneumonia secondary to Stenotrophomonas maltophila and vancomycin resistant Enteroccocus faecium. She was aggressively treated in intensive care unit but she developed multiorgan failure and died on hospital day 23.
Reactive plasmacytosis is common in AML patients with an incidence of up to 6% and can be associated with monoclonal paraproteins in the absence of other components of the diagnostic criteria of MM [19]. Therefore, it is important to rule out reactive plasmacytosis before making a diagnosis of concurrent AML and MM.
Given the rarity of the disease, there has been no established treatment and hence, prognosis remains extremely poor. Patients are often treated with therapy for AML since AML is more aggressive and anthracyclines are effective against MM as well. There are two reported cases of concurrent MM and AML in chemotherapy-naive patients, who had better outcomes compared to other patients. Raz et al describe a 68-year-old man who was diagnosed in 1978 with MM and AML without any "bizarre chromosomal changes" on cytogenetic studies. The patient was initially treated with cyclophosphamide with disappearance of monoblasts. The disease, however, recurred in 2 months when he was treated with melphalan without success and thereafter with combination chemotherapy consisting of vincristine, melphalan, cyclophosphamide and prednisone. This resulted in the disappearance of monoblasts as well as significant decline in the serum level of paraprotein. Six months later, unfortunately he developed end-organ damage related to MM and became unresponsive to chemotherapy. He died of septic shock and severe bleeding tendency 2.5 years from the time of initial diagnosis [7]. Kim et al describe a 51-year-old previously healthy man who was diagnosed with concurrent MM and AML with complex cytogenetics and immunoglobulin heavy chain rearrangement. The patient was initially treated with one-cycle of bortezomib and then with cytarabine (ara-C) and idarubicin, along with bortezomib. This was followed by re-induction with mitoxantrone and high-dose ara-C and mitoxantrone (HAM regimen) for induction failure. Because of incomplete response, the patient subsequently went on receiving myeloablative allogeneic hematopoietic stem cell transplantation (allo-SCT) after conditioning with busulfan and cyclophosphamide. The patient remains to be diseasefree and well at 421 days post-SCT [3]. There has been some promising result in a preclinical study in which tipifarnib and bortezomib have been shown to be synergistic in MM and AML cell lines [20]. Although the usefulness of these therapies needs further evaluation, because of the rarity of the disease, it will require an international registry to be able to do so.

Conclusion
Although very rare, AML and MM can present simultaneously even in chemotherapy-naive patients. Concurrent occurrence of these two malignancies portends poor prognosis. Anthracycline-based AML regimens are often used because AML is more aggressive and anthracyclines are effective against MM as well. Allogeneic stem cell transplantation as well as tipifarnib and bortezomib have shown promising re-sult.

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