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A630 Autoimmune Thrombocytopenia After Autologous Stem Cell Transplantation in a Case of Multiple Myeloma
Clinical Studies Including Transplantation biology, and their influence on prognosis and clinical outcome. We evaluated profiles of 384 microRNAs in CD138+ MM cells from 79 uniformly treated patients, 11 MM cell lines and 9 healthy donors using qRT-PCR based microRNA array and analyzed using SDS, RQ manager, and dChip softwares. We observed significant modulation of expression of 61 microRNAs in myeloma cells compared to normal plasma cells. Further, unsupervised hierarchical clustering of filtered microRNAs, identified two major groups within the MM population (group A and group B). Samples of Group A clustered with MM cell lines, indicating more proliferative cells. Within B group, a second degree node, group B2, clustered with normal plasma cells indicating indolent course. The unsupervised clustering of all MM samples showed consistent change in miR-30b-d, -142-5p, -24, -191, -181d, -374, -146b, -140, -145, -125a, 151, -223, -155, let7b, indicative of a role of these microRNA in myelomagenesis; while supervised analysis of samples within groups A and B identified modulated expression of different sets of miRNAs. In group A miR585 and let7f were upregulated 8-12 fold, while miRs -125a, -126, -155, -223, -146a, and -30d were significantly downregulated; in group B, all differentially expressed microRNAs were downregulated (P < .001) compared to normal plasma cells. These modulated miRNAs target critical signaling pathways including apoptosis, hematopoietic cell differentiation, survival, and angiogenesis by upregulating function of HOX9, c-myc, VCAM-1, Bcl-2, E2F1, SHP1, VEGF, and DUSp6. We further analyzed the effect of microRNA on clinical outcome. We have observed significantly superior event-free and overall survival of patients in group B2 compared to patients in group A (2-year estimated EFS, 79% vs. 54%, respectively; P = .05; and 2-year estimated OS 94% vs. 70%, respectively; P = .017). Taken together, this data identifies microRNAs as critical modulators of gene expression and signaling pathways and provides potential novel targets in MM to both understand biological behavior and for therapeutic application.
A629 Myeloma: 15 Years’ Experience from a Major Cancer Center in India V Raina, A Sharma, R Kumar, J Wadhwa, S Bhattacharya, S Thulkar, GK Rath, V Kocupillai Institute Rotary Cancer Hospital (IRCH), and India Institute of Medical Sciences (AIIMS), New Delhi
Introduction: The incidence of myeloma in India is 0.3-1.2 for males and 0.1-0.9/100,000 for females; This is an analysis of 524 patients that were seen over a 15 years period at IRCH, AIIMS, a tertiary cancer center in North India, and is the largest ever report from a single institution in India. Results: Myeloma constituted 10% of all cancers. Median age was 55 years (range 24-90 years). 61 patients (11.7%) were less than 40 years of age. 361 patients (69%) were between 40-60 years and males comprised 67% of patients. Only 26% patients were residents of Delhi. Mean duration of symptoms was 5 months. The stage wise distribution was Ia 6.2 %, Ib 0.2%, IIa 10.5%, IIb 1.5%, IIIa 54.5% and IIIb 27.2%. Backache was the presenting
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symptom in 69%. Anemia defined as Hb below 10g was present in 62%. In 28% serum creatinine was elevated above 2mg. Bone marrow plasmacytosis of more than 30% was seen in 59% patients. Serum electrophoresis revealed positive M spike in 85% (445/524) patients. The most common Ig isotype was IgG in 67% and ratio of kappa to lambda was 1.8:1. Mean value of M band was 3.46. Bone lesions were seen in 93%. Light chain myeloma constituted 12.80 %. Various initial treatment options used were MP, VMCP, VAD and Thal Dexa. Auto transplants as consolidation were done in 71 (13.5%). Median overall survival was 47 months and median progression free survival was 21 months. Conclusion: Important differences are seen in our patients as compared to those from the West, these are lower median age of 55 years, higher proportion of young patients; 11.7% below 40 years, more patients in advanced stage 54.5% in IIIa and 27.2% in IIIb, lower incidence of hypercalcimia. Much lower proportion of patients 13.5% underwent auto-transplants.
A630 Autoimmune Thrombocytopenia After Autologous Stem Cell Transplantation in a Case of Multiple Myeloma T Izumi Niigata University, Japan
Introduction: Autologous peripheral blood stem cell transplantation (PBSCT) for the younger patients with multiple myeloma (MM) of stage II and III (Durie-Salmon) is regarded as the standard therapy. Although thrombocytopenia may sustain after autologous PBSCT, autoimmune thrombocytopenia (AITP) in this setting appears to be rare, and the pathogenesis is unknown. Herein, we present a case of AITP after autologous PBSCT for MM, who have been monitored for more than 6 years without disease progression. Case history: A 41-year-old man was diagnosed as having MM (IgG-lambda, stage III) in April, 2001. Although radiotherapy and intensive chemotherapy (including LPAM, six courses of CHOP chemotherapy, methotrexate, cytarabine and etoposide) were performed, exacerbation were repeated. The indication of autologous PBSCT was considered for this young patient, and performed after the pretreatment by LPAM 200 mg/m2 in November, 2002 (total transfused CD34 cell number was 2.3 x 106/kg). Sustained thrombocytopenia gradually advanced, and the platelet count decreased to 1.4 x 109 per litre at day 44 after PBSCT. Bone marrow examination revealed the increase of megakaryocytes without platelet adhesion, and platelet– S 23 associated IgG (PAIgG) was a high value, so diagosis of AITP was made. Although low dose of prednisolone (PSL) therapy (0.5 mg/kg) was started, the significant rise in the platelet count was not observed 72 months after PBSCT, and high value of PAIgG remained. However, blood and urine M protein disappeared by immunofixation method after 9 months, and complete remission is sustained 72 months after PBSCT. In addition, cell surface antigen analysis performed using the peripheral blood mononuclear cells 48 and 60 months after PBSCT, the number of CD16(+) CD56 (+) lymphocytes increased. Discussion: Despite the poor prognostic characteristics, long-term disease-free survival was obtained in the present case. Further studies are needed to elucidate the relationship between the onset of AITP and antitumoral effect.
Clinical Lymphoma & Myeloma Supplement February 2009
A629 Myeloma: 15 Years’ Experience from a Major Cancer Center in India V Raina, A Sharma, R Kumar, J Wadhwa, S Bhattacharya, S Thulkar, GK Rath, V Kocupillai Institute Rotary Cancer Hospital (IRCH), and India Institute of Medical Sciences (AIIMS), New Delhi
Introduction: The incidence of myeloma in India is 0.3-1.2 for males and 0.1-0.9/100,000 for females; This is an analysis of 524 patients that were seen over a 15 years period at IRCH, AIIMS, a tertiary cancer center in North India, and is the largest ever report from a single institution in India. Results: Myeloma constituted 10% of all cancers. Median age was 55 years (range 24-90 years). 61 patients (11.7%) were less than 40 years of age. 361 patients (69%) were between 40-60 years and males comprised 67% of patients. Only 26% patients were residents of Delhi. Mean duration of symptoms was 5 months. The stage wise distribution was Ia 6.2 %, Ib 0.2%, IIa 10.5%, IIb 1.5%, IIIa 54.5% and IIIb 27.2%. Backache was the presenting
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symptom in 69%. Anemia defined as Hb below 10g was present in 62%. In 28% serum creatinine was elevated above 2mg. Bone marrow plasmacytosis of more than 30% was seen in 59% patients. Serum electrophoresis revealed positive M spike in 85% (445/524) patients. The most common Ig isotype was IgG in 67% and ratio of kappa to lambda was 1.8:1. Mean value of M band was 3.46. Bone lesions were seen in 93%. Light chain myeloma constituted 12.80 %. Various initial treatment options used were MP, VMCP, VAD and Thal Dexa. Auto transplants as consolidation were done in 71 (13.5%). Median overall survival was 47 months and median progression free survival was 21 months. Conclusion: Important differences are seen in our patients as compared to those from the West, these are lower median age of 55 years, higher proportion of young patients; 11.7% below 40 years, more patients in advanced stage 54.5% in IIIa and 27.2% in IIIb, lower incidence of hypercalcimia. Much lower proportion of patients 13.5% underwent auto-transplants.
A630 Autoimmune Thrombocytopenia After Autologous Stem Cell Transplantation in a Case of Multiple Myeloma T Izumi Niigata University, Japan
Introduction: Autologous peripheral blood stem cell transplantation (PBSCT) for the younger patients with multiple myeloma (MM) of stage II and III (Durie-Salmon) is regarded as the standard therapy. Although thrombocytopenia may sustain after autologous PBSCT, autoimmune thrombocytopenia (AITP) in this setting appears to be rare, and the pathogenesis is unknown. Herein, we present a case of AITP after autologous PBSCT for MM, who have been monitored for more than 6 years without disease progression. Case history: A 41-year-old man was diagnosed as having MM (IgG-lambda, stage III) in April, 2001. Although radiotherapy and intensive chemotherapy (including LPAM, six courses of CHOP chemotherapy, methotrexate, cytarabine and etoposide) were performed, exacerbation were repeated. The indication of autologous PBSCT was considered for this young patient, and performed after the pretreatment by LPAM 200 mg/m2 in November, 2002 (total transfused CD34 cell number was 2.3 x 106/kg). Sustained thrombocytopenia gradually advanced, and the platelet count decreased to 1.4 x 109 per litre at day 44 after PBSCT. Bone marrow examination revealed the increase of megakaryocytes without platelet adhesion, and platelet– S 23 associated IgG (PAIgG) was a high value, so diagosis of AITP was made. Although low dose of prednisolone (PSL) therapy (0.5 mg/kg) was started, the significant rise in the platelet count was not observed 72 months after PBSCT, and high value of PAIgG remained. However, blood and urine M protein disappeared by immunofixation method after 9 months, and complete remission is sustained 72 months after PBSCT. In addition, cell surface antigen analysis performed using the peripheral blood mononuclear cells 48 and 60 months after PBSCT, the number of CD16(+) CD56 (+) lymphocytes increased. Discussion: Despite the poor prognostic characteristics, long-term disease-free survival was obtained in the present case. Further studies are needed to elucidate the relationship between the onset of AITP and antitumoral effect.
Clinical Lymphoma & Myeloma Supplement February 2009