C-MYC Rearrangement: A Marker for High-Risk Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4989-4989
Author(s):  
Isabella C. Glitza ◽  
Gary Lu ◽  
Su Chen ◽  
Robert Z. Orlowski ◽  
Muzaffar H. Qazilbash
Keyword(s):  
Stem Cell ◽  
Plasma Cell ◽  
Response To Therapy ◽  
Chromosome 8 ◽  
Plasma Cell Leukemia ◽  
Disease Stage ◽  
High Dose ◽  
Cell Leukemia ◽  
Hematopoietic Stem ◽  
Conventional Cytogenetics

Abstract Abstract 4989 Background: The proto-oncogene c-MYC encodes a transcription factor that regulates cell proliferation, growth, and apoptosis. c-MYC is mapped to the 8q24. 1 on the long arm of chromosome 8 and its rearrangement has been reported in 15% of myeloma patients independent of the disease stage (Avet-Loiseau et al. Blood 2001). However, the clinical significance of c-MYC rearrangement is not well described. Here we report the characteristics and outcome of myeloma patients with c-MYC rearrangements that were treated at our institution. Methods: We identified 18 patients (11 males, 7 females) with c-MYCrearrangements either on fluorescence in situ hybridization (FISH) analyses or conventional cytogenetics, who were treated at the M.D. Anderson Cancer Center. The primary objective was to describe the patient characteristics, response to therapy, time to progression (TTP), and overall survival (OS). Results: Median age at diagnosis was 56. 5 years (21–72). Overall, 8 patients (44%) presented with or progressed to either plasma cell leukemia (PCL: 6) or plasmablastic myeloma (PBM: 2). Abnormalities involving chromosome 8q24. 1, the c-MYC locus, were detected on conventional cytogenetics in all 18 patients, including t(8;14)(q24. 1;q32) in 6 cases, t(2;8)(p12;q24. 1) in 3 cases, t(8;22) (q24. 1;q11. 2) in 4 cases, t(8;20)(q24. 1;q13. 3) in one case, and an abnormal chromosome 8 with unknown material attached to the 8q24. 1 region in 4 cases. Five patients (27%) had a del(13)(q14. 1)/RB1, one of whom had a del(17)(p13)/TP53, while 3 other patients had t(11;14)(q13;q32) involving CCND1-XT/IGHrearrangements. Twelve patents (66%) received induction with a novel agent: bortezomib-based = 8 (44%) and thalidomide- based = 4 (22%). Six patients (33%) received induction with conventional chemotherapy regimens: CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) = 2, pulsed steroids only = 2, EPOCH (Etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide) = 1 and melphalan + prednisone =1. Nine patients achieved a partial response (PR, 50%) and 4 patients achieved a very good partial remission (VGPR, 22%), with an overall response rate of 72% to induction. Thirteen patients (72%) went on to receive high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT). Four patients died of disease progression before auto-HCT while one patient opted for stem cell harvest and cryopreservation only. Median time to auto-HCT was 7. 1 months (3. 6–12. 7). Median follow up in all patients was 13 months (range 3. 4–105). Fifteen patients had progressed, with a median TTP of 7. 1 months and a median OS of 20. 2 months. Patients with PCL or PBM had significantly shorter OS (p=0. 04). Conclusion: This is the first report describing clinical characteristics of myeloma patients with c-MYC rearrangements. c-MYC rearrangement is associated with a higher incidence of plasma cell leukemia or plasmablastic myeloma, short TTP and OS. Disclosures: No relevant conflicts of interest to declare.

Clinical Features of Patients with Multiple Myeloma and C-MYC Rearrangements

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5090-5090
Author(s):  
Isabella C. Glitza ◽  
Gary Lu ◽  
Su Chen ◽  
Robert Z. Orlowski ◽  
Muzaffar Qazilbash
Keyword(s):  
Conflicts Of Interest ◽  
Primary Objective ◽  
Response To Therapy ◽  
Chromosome 8 ◽  
Disease Stage ◽  
Bone Lesions ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Conventional Cytogenetics

Abstract Abstract 5090 Background: The proto-oncogene c-MYC encodes a transcription factor that regulates cell proliferation, growth, and apoptosis. c-MYC is located on the long arm of chromosome 8 (8q24.1) and its rearrangement has been reported in 15% of myeloma patients independent of the disease stage (Avet-Loiseau et al. Blood 2001). However, the clinical significance of c-MYC rearrangement is not well described. Here we report the characteristics and outcome of 7 myeloma patients with c-MYC rearrangements that were treated at our institution. Methods: Between July 2007 and May 2011, we identified 7 patients (4 males, 3 females) who had c-MYC rearrangements on fluorescence in situ hybridization (FISH) analyses at the time of diagnosis. The primary objective of this study was to describe the patient characteristics, response to therapy, time to progression (TTP), and overall survival (OS). Results: Median age at diagnosis was 58 years (49–72). There were 4 Caucasians, 2 African-Americans and 1 Asian. International Staging System stage was I, II, and III in 3, 2, and 2 patients, respectively. Two patients had serum creatinine of ≥2 mg/dL as well as Hgb ≤10 g/dL, two other patients had hypercalcemia at diagnosis. Six (85%) patients had myelomatous bone lesions at diagnosis. Plasma cell counts in bone marrows ranged from 20%-78%, with a mean of 51%. Abnormalities involving chromosome 8q24.1, the c-MYC locus, were detected on conventional cytogenetics in all 7 patients, including t(8;14)(q24.1) in 3 cases, a t(2;8)(p12;q24.1), a variant of the t(8;14), in 2 cases, and an abnormal chromosome 8 with unknown material attached to the 8q24.1 region confirmed by FISH in two cases. This is in contrast to an earlier report where only 25% of patients with c-MYC rearrangement on FISH had corresponding cytogenetic abnormalities. Three patients also had a del(13)(q14.1)/RB1, one of whom also had a del(17)(p13)/TP53, while two other patients had t(11;14)(q13;q32) involving CCND1-XT/IGH rearrangements. Six patients (85%) received induction with a bortezomib+ dexamethasone regimen, and one patient received thalidomide+ dexamethasone. Five patients achieved a partial (PR) or very good partial remission (VGPR) to induction, while 2 patients had <PR, with an overall response rate of 71%. Four patients went on to receive high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT). Three of these patients were in first remission, while one patient progressed prior to auto-HCT. Median follow up in all patients was 17.7 months (range 2.6–22.4). Two patients progressed at 4.4 and 4.5 months after the start of induction therapy, and 2 more patients progressed after auto-HCT, 14.4 and 16.1 months after the start of induction. Median TTP was 14.4 months, and median OS was 20.2 months. The TTP and OS appear to be shorter than what has been reported for standard-risk myeloma patients (24 and 72 months, respectively). Conclusion: This is the first report describing clinical characteristics of myeloma patients with c-MYC rearrangements. All 7 patients had concurrent translocations involving chromosome 8q24 on conventional cytogenetics, and had a shorter TTP and OS than our historical data. The role of c-MYC rearrangement in myeloma needs to be explored in prospective studies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Relapsed/refractory multiple myeloma-transformed plasma-cell leukemia successfully treated with daratumumab followed by autologous stem cell transplantation

2021 ◽  
Vol 12 ◽  
pp. 204062072198957
Author(s):  
Chen-lu Yang ◽  
Neng-gang Jiang ◽  
Li Zhang ◽  
Kai Shen ◽  
Yu Wu
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Plasma Cell ◽  
Immune Cell ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia ◽  
Hematopoietic Stem ◽  
Refractory Multiple Myeloma

Daratumumab is a humanized anti-CD38 IgG1 monoclonal antibody which could be used for multiple myeloma (MM). MM with plasma-cell leukemia (PCL) transformation is highly aggressive and is resistant to conventional therapy. Novel therapeutics are needed for PCL, and daratumumab may play role. We report a case of relapsed/refractory multiple myeloma (RRMM)-transformed PCL successfully treated with daratumumab. The case was a 42-year-old man who was diagnosed with MM 2 years ago and relapsed after six cycles of bortezomib-based chemotherapy. The patient rapidly developed hyperleukocytosis and disseminated intravascular coagulation, and was diagnosed with PCL. Daratumumab-based therapy was tried and the case miraculously obtained complete remission (CR) after four doses of a weekly infusion of daratumumab. Finally the patient received autologous hematopoietic stem-cell transplantation (auto-HSCT) and maintained CR. Moreover, we monitored the immune cell dynamics by flow cytometry (FCM) during daratumumab-based treatment. The immune cell subset analysis revealed significant down-regulation of CD38+ natural killer (NK) cells, regulatory T cells (Tregs) and regulatory B cells (Bregs). Meanwhile cytotoxic T-lymphocyte expansion was observed. In conclusion, daratumumab could rapidly decrease tumor burden, improve the condition of the PCL patient, and serve as a bridging salvage chemotherapy for further chimeric antigen recptor T cell therapy (Car-T) or HSCT, which could potentially improve patient survival. The immune cell dynamic findings in this case suggest that the immunomodulatory mechanism may contribute to the antimyeloma effect of daratumumab.

scholarly journals Primary Plasma Cell Leukemia: Stem Cell Transplant in an Era of Novel Induction Drugs

2018 ◽  
Vol 24 (3) ◽  
pp. S260-S261 ◽  
Author(s):  
Lohith Gowda ◽  
Mithun Vinod Shah ◽  
Ifra Badar ◽  
Qaiser Bashir ◽  
Nina Shah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Plasma Cell ◽  
Stem Cell Transplant ◽  
Plasma Cell Leukemia ◽  
Cell Transplant ◽  
Cell Leukemia ◽  
Leukemia Stem Cell ◽  
Primary Plasma Cell Leukemia

scholarly journals Plasma cell leukemia: Detailed studies and response to therapy

Cancer ◽  
1974 ◽  
Vol 33 (3) ◽  
pp. 619-625 ◽  
Author(s):  
Michael T. Shaw ◽  
Thomas W. Twele ◽  
Robert E. Nordquist
Keyword(s):  
Plasma Cell ◽  
Response To Therapy ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia

Primary Plasma Cell Leukemia: Results of a Retrospective Italian Multicentric Survey.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2885-2885
Author(s):  
Livio Pagano ◽  
Caterina Giovanna Valentini ◽  
Valerio De Stefano ◽  
Adriano Venditti ◽  
Giuseppe Visani ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Alkylating Agents ◽  
Plasma Cell Leukemia ◽  
High Dose ◽  
Cell Leukemia ◽  
Front Line ◽  
Line Therapy ◽  
Primary Plasma Cell Leukemia

Abstract Abstract 2885 Poster Board II-861 Background: Epidemiological and clinical information on Primary Plasma Cell Leukemia (pPCL) are rarely reported. Aims: To evaluate in patients (pts) with pPCL the clinical features, the prognostic factors, and the efficacy of treatments. Patients and Methods: A multicenter retrospective cohort study was carried out between January 2000 and December 2008 in 26 Italian hematology divisions. A total of 128 cases of PCL were collected, and 73 of them (57%) were classified as primary (M/F 43/30). Results: The median age was 63 years (range 32-86). At diagnosis the median values of peripheral blood plasma cells and bone marrow plasma cell infiltration were 2.7 × 10 9/L (range 0.4-49.9) and 80% (range 37-100), respectively. The median values of hemoglobin, white blood cell count, and platelet counts were 9.1 g/dl (range 4.8-12.9), 13.7 × 10 9/L (range 1.3-56.7), 116 × 10 9/L (range 8-428), respectively. Extramedullary disease was present in ten cases (14%) and included testis, muscular, neuromeningeal, and cutaneous localization. At diagnosis, 64 pts (88%) had at least one CRAB sign, namely 35 pts (48%) had low hemoglobin level, 20 pts (27%) calcium ≥11 mg/dl, 32 pts (44%) creatinine ≥2 mg/dl, and 47 pts (64%) had osteolysis. In 41 pts (56%) cytogenetic study was performed, revealing an unfavourable karyotype in 17 (23%), in 13 of them del(13q-). Seventy-two pts received front-line therapy (1 died early, receiving only support treatments and steroids), that included antracycline-containing regimens in 36 pts (50%), and single alkylating agents in 17 pts (24%, 9 cyclofosfamide and 8 melphalan). In 11 of them Bortezomib (BTZ, n= 7) or Thalidomide (THAL, n= 4) were also employed. Finally, 19 pts (26%) received BTZ (4) or THAL (5) or both (10) as unique treatment. Twenty-one pts (29%) underwent autologous stem cell transplantation (SCT) as part of front-line therapy, followed by allogeneic-SCT in four cases; two additional pts underwent only allogeneic-SCT. A complete or partial remission after front-line therapy was achieved in 20 pts (27%) and 19 pts (26%) respectively (overall response rate 53%). The median overall survival (OS) was 13.1 months (range 0.5-75.8); 30.6 months (range 4.7-75.8) in responder pts and 4.2 months in non-responder ones (range 0.5-75.6, univariable hazard ratio, HR, 0.28, 95% CI 0.11-0.39). In the responder pts the median progression free survival (PFS) was 17.2 months (range 1.4-72.1). Of note, in SCT pts the median OS and PFS were 38.1 months (range 4.8-75.8) and 25.8 months (range 1.4-72.1) respectively, with a significant advantage with respect to non-transplanted pts in OS (median 9.1 months, range 0.5-75.6, HR 0.28, 95% CI 0.16-0.52) and in PFS (median 7.3 months, range 1.7-17.7, HR 0.29, 95% CI 0.04-0.44). The low number of allo-SCTs did not allow a reliable separate statistical analysis. A multivariable Cox proportional hazard regression analysis showed that OS was influenced by lack of initial response (HR 2.62, 95% CI 1.04-6.57), albumin <3 g/dl (HR 3.33, 95% CI 1.64-6.76), and SCT (HR 0.34, 95% CI 0.12-0.98). Pts with hypercalcemia at diagnosis had a shorter PFS (HR 4.0, 95% CI 1.04-15.24); the PFS was favourably influenced by SCT (HR 0.05, 95% CI 0.009-0.28). Overall, the use of BTZ and/or THAL did not influence the OS and PFS. Conclusions: pPCL is a highly aggressive lymphoprolipherative malignancy, characterized by a poor prognosis and a low response rate to conventional therapy. The use of high-dose chemotherapy followed by autologous or allogeneic-SCT is a very effective therapy leading to 66% increase in the OS and to 95% increase in PFS in respect to non-transplanted pts. Apparently, the use of novel drugs such as BTZ and THAL did not produce a further amelioration in the patient outcome. However, those latter findings should be taken with caution, given the relatively low number of treated pts. Disclosures: No relevant conflicts of interest to declare.

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