Dual Diagnosis of Multiple Myeloma and T-cell Large Granular Lymphocytic Leukemia: A Case Report and Literature Review

Case Report

Ann Hematol Oncol. 2015; 2(9): 1062.

Dual Diagnosis of Multiple Myeloma and T-cell Large Granular Lymphocytic Leukemia: A Case Report and Literature Review

Carreau NA¹, Lee JY², Petersen B¹, Silverman L¹ and Chari A¹*

¹Mount Sinai Medical Center, USA

²Columbia University Medical Center, USA

*Corresponding author: Ajai Chari, Affiliated with Mount Sinai Medical Center, 1 Gustave Levy Place, Box 1185, New York, NY 10029, USA

Received: November 03, 2015; Accepted: December 10, 2015; Published: December 12, 2015

Abstract

A 52 year-old Caucasian male with stable Crohn’s disease off medications, with anemia and known vitamin B12 and iron deficiency, was noted to be pancytopenic with a white blood cell count of 1,600/uL and a platelet count of 106,000/uL. He also noted night sweats, fatigue, and a distended abdomen. While admitted with febrile neutropenia due to methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia in the setting of a rectal abscess, further workup revealed a new diagnosis of lambda light chain multiple myeloma (MM). After 4 cycles of chemotherapy, he achieved a partial response but remained cytopenic and developed increased splenomegaly. Extensive workup resulted in the diagnosis of T-cell large granular lymphocytic leukemia (T-LGLL) by T-cell receptor gene rearrangement studies. Initiation of oral cyclophosphamide with corticosteroids resulted in improvement in blood counts, and he was consolidated with an allogeneic stem cell transplant. His MM appeared to be in a stringent complete remission at 30 months, whereas the T cell rearrangement for T-LGLL was initially negative but then became positive again 7 months later.

T –LGLL is a clonal disease of large granular lymphocytes, typically cytotoxic T cells, which accounts for 2-3% of all cases of chronic lymphoproliferative disorders. Common symptoms include fever, recurrent bacterial infections, weight loss, and fatigue. Labs usually note cytopenias, and both splenic and hepatic involvement are common. T-LGLL is often associated with autoimmune disorders, and may co-exist with other hematologic malignancies, seldomly with a primary diagnosis of multiple myeloma (MM). Given the rarity of the disease and its typically indolent course, there are no standard treatment guidelines, and immunosuppressive chemotherapy is reserved for cases of symptomatic cytopenias and splenomegaly. In an era with increasing concerns about secondary malignancies in MM, the differential for patients with persistent cytopenias and/or splenomegaly despite treatment should include concomitant T-LGLL.

Keywords: T-LGLL; Multiple myeloma; Splenomegaly; Cytopenia

Case Presentation

A 52 year-old Caucasian male with Crohn’s disease stable off medications for several years, with anemia and known vitamin B12 and iron deficiency, was noted to be pancytopenic with a white blood cell (WBC) count of 1,600/uL and a platelet count of 106,000/uL for two months. The patient endorsed night sweats over the preceding two years, a distended abdomen for six months, and recent fatigue. He then developed 15 days of fever and was found to be neutropenic with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia in the setting of a rectal abscess.

Initial labs revealed a WBC count of 1,200/uL, with only 6% segmented cells, 38% lymphocytes, 26% eosinophils, 12% monocytes and 16% basophils, with an absolute neutrophil count of 72/uL without bands. Hemoglobin was 8.9 g/dL (MCV 80 fl), platelet count241,000/ uL, creatinine 0.79 mg/dL, calcium 8.5/mL, total protein 5.4 mg/dL, albumin 2.6 mg/dL, and beta-2-microglobulin 4.51 mg/L.ESR was elevated to 87 mm/hr and CRP 28.1 mg/L. Chemistry revealed mild hypokalemia, and hepatic function tests were normal.

The Immunoglobulin G (IgG) and IgA were within normal limits at 1066 mg/dL and 342 mg/dL respectively, but IgM was low at 6 mg/ dL (normal 40-320). Serum protein electrophoresis (SPEP) revealed two monoclonal bands in the gamma region too low to quantitate. Serum immunofixation electrophoresis (SIFE) revealed a free monoclonal lambda light chain and faint IgG lambda band. 24h urine protein electrophoresis (UPEP) revealed 12.4 g proteinuria with 10.1 g Bence Jones protein (BJP) identified on urine immunofixation electrophoresis (UIFE) as lambda light chains. Serum free kappa chains were 25.05 mg/L and serum free lambda chains were 2034 mg/L (normal 5.71-26.30 mg/L), with a kappa: lambda ratio of 0.012 (normal 0.26-1.65).

Initial bone marrow (BM) biopsy revealed 10% lambda-restricted plasma cells. Repeat biopsy showed a mildly hypercellular marrow with patchy infiltrates of lambda light chain restricted CD 138 positive plasma cells comprising 20% of the bone marrow cellularity, consistent with lambda light chain MM. Cytogenetics and FISH were normal.

Positron emission tomography-computed tomography (PETCT) revealed diffuse uptake in the BM of the axial and appendicular skeleton without focal or osteolytic lesions, in addition to bilateral hypermetabolic inguinal, axillary, and mesenteric lymph nodes up to 1.2 cm in size. Hepatomegaly at 22 x 16 cm and splenomegaly at 20 cm in long axis without abnormal FDG uptake were also seen. The patient was diagnosed with lambda light chain multiple myeloma, Durie-Salmon Stage 3A due to nadir Hg 7.4 and International Staging System (ISS) Stage 2.

Bortezomib was given subcutaneously on days 1,4,8, and 11 along with dexamethasone 40 mg orally on the same days. Thalidomide 100mg then 200mg was added to cycles 2 through 4 with a partial response (PR). Due to sensory neuropathy, thalidomide was replaced with cyclophosphamide 250mg/m2 IV (dose reduced for cytopenias) on days 1 and 8. After a total of 5 cycles of chemotherapy, 24hour UPEP revealed a 61.5% reduction in BJP consistent with stable disease (SD).

BM biopsy was repeated to re-evaluate myelosuppression given the need for granulocyte colony-stimulating factor (G-CSF) support throughout induction chemotherapy with a relatively non-myelosuppresive regimen. This revealed a hypercellular (70%) marrow with trilineage hematopoiesis showing full maturation, with 10-20% plasma cells and no evidence of myelodysplasia. Cytogenetics and flow cytometry were unrevealing.

The patient suffered a subacute ischemic frontoparietal stroke with a platelet count of 60,000/uL, and subsequent paroxysmal nocturnal hemoglobinuria testing was negative. Repeat PET-CT revealed increased splenomegaly to 22cm x 13cm (Figure 1). Testing for Gaucher’s disease, Felty’s syndrome (with rheumatoid factor), autoimmune disease (with antinuclear antibodies), and amyloid (with congo red stain of BM, fat pad, liver and rectum) was negative. G-CSF and plerixafor based stem cell harvest was attempted twice with a combined yield of only 2.37* 10^6 CD34+/kg.

Citation: Carreau NA, Lee JY, Petersen B, Silverman L and Chari A. Dual Diagnosis of Multiple Myeloma and T-cell Large Granular Lymphocytic Leukemia: A Case Report and Literature Review. Ann Hematol Oncol. 2015; 2(9): 1062. ISSN : 2375-7965