Hematology Reports 2016; volume 8:6295 Immunoglobulin D multiple Case Report Correspondence: Naveed Ali, Abington Memorial myeloma, plasma cell leukemia Hospital/Abington-Jefferson Health, Department and chronic myelogenous An 88-year-old male urologist with a history of Internal Medicine, 1200 Old York Road, leukemia in a single patient of atrial fibrillation, iron deficiency anemia Abington, 19001 PA, USA. and unprovoked pulmonary thromboembolism, Tel.: +1.267.471.0165 - Fax: +1.215.481.4361. treated simultaneously with presented to our hospital in January 2014 after E-mail: [email protected] lenalidomide, bortezomib, a fall leading to rhabdomyolysis and quadri- Key words: Immunoglobulin D multiple myeloma; dexamethasone and imatinib ceps tendon rupture. Upon laboratory investi- plasma cell leukemia; chronic myelogenous gations, he was found to have normocytic nor- leukemia; bortezomib; imatinib. Naveed Ali,1 Peter V. Pickens,2 mochromic anemia with a hemoglobin level of Herbert E. Auerbach3 9.8 g/dL, mean corpuscular volume of 94.3 fl Contributions: the authors contributed equally. and reticulocyte count of 2.3%. White blood cell 1 Departments of Internal Medicine, count was 14.6×103 per µL (58% neutrophils, Conflict of interest: the authors declare no poten- 2 3 Hematology and Oncology, Pathology, 12% lymphocytes, 30% monocytes, 0% tial conflict of interest. Abington Memorial Hospital/Abington- basophils and 0% eosinophils) and platelet Jefferson Health, PA, USA count was 191×103 per µL. Absolute monocyte Received for publication: 4 November 2015. count was elevated at 4.4×103 per µL (normal Revision received: 19 January 2016. Accepted for publication: 19 January 2016. range 0.0-0.9×103 per µL). Iron deficiency ane- mia and megaloblastic anemia due to hypovit- This work is licensed under a Creative Commons Abstract aminosis B12 or folate were excluded. Attribution-NonCommercial 4.0 International Presence of anemia and persistent monocyto- License (CC BY-NC 4.0). Multiple myeloma (MM) is a neoplastic lym- sis suggested underlying bone marrow pathol- ogy such as myelodysplasia or chronic ©Copyright N. Ali et al., 2016 phoproliferative disorder characterized by Licensee PAGEPress, Italy uncontrolled monoclonal plasma cell prolifera- myelomonocytic leukemia, and warranted a bone marrow examination. onlyHematology Reports 2016; 8:6295 tion. Among different isotypes of MM, doi:10.4081/hr.2016.6295 immunoglobulin D (IgD) MM is very rare, rep- A bone marrow aspirate and biopsy showed resenting only 1 to 2% of all isotypes. Chronic mild trilineage hypercellularity with myeloid to erythroid cell ratio of 4.7:1; however monocytes myelogenous leukemia (CML) is a neoplastic kappa smoldering multiple myeloma (Durie- were not noted to be elevated (Figure 1A-C). myeloproliferative disorder of pluripotent use Salmon stage I and International Staging Immunohistochemical stains demonstrated 15 hematopoietic stem cell, which is character- System I) and chronic phase chronic myel- CD138 positive, CD20 positive, monoclonal ized by the uncontrolled proliferation of ogenous leukemia simultaneously. Therapy kappa plasma cells accounting for 10% cellular- myeloid cells. An 88-year-old male was diag- was not initiated and a watch and wait ity (Figure 1D,E). Flow cytometry demonstrat- nosed simultaneously with IgD kappa MM and approach was implemented with serial clinical ed plasma cells positive for kappa chain, CD38, CML. A distinctive feature in this patient was and laboratory assessments. CD138, CD20, partial CD45, dim CD27 and the progression to plasma cell leukemia with- In May 2014, after two months of initial CD200, and negative for CD19, CD56, CD117, out any symptomatic myeloma stage. He was diagnosis, he developed profound fatigue, CD28 and CD81. Cytogenetic analysis by FISH treated simultaneously with lenalidomide, severe nocturnal sweating and low grade (fluorescence in situ hybridization) demon- bortezomib and imatinib. Synchronous occur- fevers. On laboratory evaluation, he had a sud- strated translocation t(11;14) (Figure 1F) and den increase in white blood cell count to rence of these rare hematological malignan- deletion chromosome 17p13 (TP53) but did not 40×103 per µL, increase in serum kappa chain cies in a single patient is an exceedingly rare commercialdetect rearrangements of chromosome 1p or level and decrease in immunoglobulin levels event. Multiple hypotheses to explain co-occur- 1q, gain of chromosome 5q, deletion of chro- (Table 1). A peripheral blood smear examina- rence of CML and MM have been proposed; mosome 13 (or 13q), t(14;16) or t(4;14). tion showed presence of circulating plasma however, the exact etiological molecular patho- Unexpectedly, karyotype analysis detected cells, plasmacytoid lymphocytes and abnormal physiology remains elusive. Non Philadelphia chromosome [t(9;22)(q34;q11)] lymphocytes which were previously not pres- in 8 out of 20 metaphases analyzed (Figure ent (Figure 1H). He had rapidly progressed 1G). Serum protein electrophoresis and from an asymptomatic smoldering myeloma immunofixation showed immunoglobulin D stage to PCL. Introduction kappa monoclonality with M-spike of 1 g/dL. A Therapy for MM and PCL was instituted as skeletal survey was unremarkable for any char- RVD (lenalidomide, bortezomib and dexam- Multiple myeloma (MM) has an annual inci- acteristic myeloma bony lesions, as was mag- ethasone) regimen that resulted in disappear- dence of 5.6 cases per 100,000 individuals in netic resonance imaging of the spine. Serum ance of plasma cells from peripheral circula- the US.1 Chronic myelogenous leukemia calcium and renal function were normal. tion. Imatinib for treatment of CML was not (CML) has an annual incidence of 1-2 cases Serum free kappa chains were elevated with started along with RVD to avoid potentially per 100,000 individuals.2-4 Co-occurrence of an increased kappa:lambda chain ratio (Table dangerous adverse effects from combined pro- these two disorders in one patient is an 1). Immunoglobulin levels were depressed teasome inhibitor and tyrosine kinase extremely rare event, described in a handful of except for markedly elevated immunoglobulin inhibitor therapy given patient’s advanced age cases in the literature.4-14 We describe an D level (Table 1). At the same time, quantifica- and co-morbidities. However, he exhibited exceedingly rare case of simultaneous tion of chimeric BCR-ABL mRNA transcripts worsening leukocytosis and thrombocytosis immunoglobulin D kappa MM with plasma cell was done by reverse transcription polymerase with counts as high as 90×103 per µL and leukemia (PCL) and CML which, to our knowl- chain reaction (RT-PCR). There were no plas- 2069×103 per µL, respectively. BCR-ABL mRNA edge, has not been reported in the literature. ma cells detected on peripheral smear exami- transcripts were found elevated at 180.38%. He nation. He was therefore diagnosed with IgD was subsequently started on imatinib (400 mg [Hematology Reports 2016; 8:6295] [page 1] Case Report daily) for CML. Both RVD and imatinib were ment in free kappa chain, LDH, BCR-ABL ued to decline. In September 2014, he was continued which he tolerated well with diar- mRNA transcripts and immunoglobulin D lev- admitted to the hospital and succumbed to ful- rhea as the only side effect which was well con- els. A trend of myeloma parameters longitudi- minant septic shock consequent to pneumo- trolled with antidiarrheal medication. nally over time is summarized in Table 1. A nia. Over the next few weeks, he demonstrated complete clinical remission, however, was not subjective improvement as well as improve- achieved. The immunoglobulin levels contin- Table 1. Laboratory myeloma parameters. Smoldering MM MM/PCL (therapy initiated) Follow-up on treatment M-spike, g/dL 1 1 0 Free kappa chain level (normal range 3.3-19.4 mg/L) 99.5 107.2 21.5 Free lambda chain level (normal range 5.7-26.3 mg/L) 6.4 8.1 10.8 Free kappa/lambda ratio (normal range 0.26-1.65) 15.55 13.23 1.99 Beta 2 microglobulin (normal <2.51 mg/L) 2.56 3.53 4.61 LDH (normal range 120-250 U/L) 258 595 209 Immunoglobulin G (normal range 694-1618 mg/dL) 433 312 267 Immunoglobulin A (normal range 81-463 mg/dL) 65 34 31 Immunoglobulin M (normal range 48-271 mg/dL) 49 38 32 Immunoglobulin D (normal <179 mg/L) 4640 3570 152 MM, multiple myeloma; PCL, plasma cell leukemia; LDH, lactate dehydrogenase Table 2. Characteristics of cases of coexisting multiple myeloma and chronic myelogenous leukemia. Light chain Case Age/ Sex Chronological Treatment only report order Immunoglobulin G 5 κ Pessach et al. 63/F CML → MM CML: Imatinib, MM: bortezomib,use lenalidomide, dexamethasone 5 λ Pessach et al. 68/M MM → CML MM: Vincristine, doxorubicin, dexamethasone, radiation, zoledronic acid, CML: imatinib 6 κ Alsidawi et al. 60/M MM → CML MM: Radiation, lenalidomide, bortezomib, dexamethasone, CML/ AML – hydroxyurea, dasatinib 7 κ Ragupathi et al. 62/F MM → CML MM: Radiation, dexamethasone, bortezomib, cyclophosphamide, doxorubicin, lenalidomide, CML: dasatinib 8 κ Offiah et al. 71/F MM + CML CML: Imatinib, MM: melphalan, prednisolone, bortezomib, dexamethasone, lenalidomide, cyclophosphamide 9 κ Ide et al. 72/F CML → MM CML: Imatinib, MM: no treatment 12 λ Garipidou et al. 68/M CML → MM CML: INF-alpha, imatinib, MM: malphalan and prednisolone 5 λ Wakayama et al. 85/F MM + CML 13 κ Shwarzmeier et al. 66/M CML +commercial MM CML: Hydroxyurea, IFN-alpha, busulfan, MM: melphalan and prednisolone 5,7 κ Nitta et al. 70/M MM → CML CML: Hydroxycarbamide, MM: Not reported 5,7 κ Tanaka et al. 72/F CML + MM CML: INF-alpha, hydroxycarbamide, MM: INF-alpha, Vindesine sulfate, prednisolone 5,7 κ Klenn et al. 71/M MM → CML MM: Radiation, malphalan, prednisone, CML: Hydroxyurea 5,7 κ Boots et al. 58/MNon CML + MM MM: Radiation, malphalan, prednisone, CML: hydroxyurea, busulfan, thioguanine 5,7 κ Derghazarian et al. 65/F CML → MM MM and CML: busulphan, Radiation, phenylalanine mustard Immunoglobulin A 4 λ Maerki et al.