Cytogenetics and Clinical Outcomes of Plasma Cell Leukemia Patients: A Single Institution Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4932-4932
Author(s):  
Daniel J. Lebovic ◽  
Rachid Baz ◽  
Melissa Alsina ◽  
Jose L Ochoa ◽  
Daniel Sullivan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Response To Therapy ◽  
Plasma Cell Leukemia ◽  
Novel Agents ◽  
Cell Leukemia ◽  
Allogeneic Transplant ◽  
The Impact

Abstract Abstract 4932 Introduction Plasma cell leukemia (PCL) is a rare, poorly understood and clinically aggressive plasma cell dyscrasia that can originate from multiple myeloma (sPCL) or de novo as primary PCL (pPCL). Historically, median survival of patients with PCL has been reported to be 1 and 11 months for patients with secondary and primary PCL, respectively (Tiedemann, Leukemia 2008). The impact of novel agents and transplantation strategies on outcomes of patients with PCL remains unclear. In addition, few have reported extensively on the cytogenetics abnormalities seen in patients with PCL especially with respect to outcomes with novel therapies (proteasome inhibitor or immunomodulator). Accordingly, we thought to evaluate the clinical, cytogenetic features and outcomes of patients with PCL treated at H. Lee Moffitt Cancer Center in the era of novel agents and transplant strategies. Materials and Methods Retrospective review of records of patients with PCL diagnosed after 2003. The diagnosis of PCL was according to the IMWG criteria (specifically peripheral blood plasma cells ≥ 20% or 2 ×109/L). Clinical data reviewed included basic demographic, laboratory, pathologic, treatment and outcomes variables. Cytogenetics was reviewed by metaphases and FISH. Overall survival was defined as the time from diagnosis of PCL to death or last follow-up. Response criteria was according to the IMWG. Treatment was at the discretion of the treating physician. Results Twenty four patients with PCL were identified: 15 patients had pPCL and 9 had sPCL. The median age of all patients was 58 years (range 37-77years). The median peripheral WBC was 15×109/L (range 3-102 ×109/L) and the median percent of peripheral plasma cells was 40% (15-93%). The median β2 microglobulin was 3 mg/L (range 1.4-23). Nine patients (38%) had renal failure (creatinine>2.0mg/L) at diagnosis of PCL and 11/19 (58%) had a serum LDH greater than the institution's upper limit of normal. Two patients had CNS disease and 6 patients had extramedullary disease. Regarding metaphase cytogenetics: One patient had a novel translocation involving 3 separate breakpoints, which included: ins(6;14)(p22;q32q32)t(6;11)(p22;q13), der (14) ins (11)(q32;q13q13)?? t(6;14)(p22;q32), 3 patients (2 with pPCL) had a translocation between chromosomes 1 and 16 including t(1;16)(q21;q24), t(1;16)(q21;22) and t(1;16)(break points not reported). 14/23 patients with PCL (61%) had deletion of chromosome 13 by either FISH or cytogenetics; while 80% of patients with pPCL (12/15) had 13q deletion. Only one patient had deletion 17p. 11 patients received bortezomib based therapy and 19 patients received a novel agent, 5 had an allogeneic transplant, 19 had high dose therapy and autologous transplantation). Best response to therapy was as follows: 9 CR, 4 VGPR, 4PR, 1MR, 2 Non evaluable (PR and better: 77%). After a median follow up of 13 months, 5 remain alive (all had autologous transplant and 3 had an allogeneic transplant) (median follow up 2 years; range 2-34 months). The median overall survival for pPCL compared to sPCL via Kaplan-Meier was 28.4 vs. 3.5 months, respectively (p=0.0018). See Figure 1. Conclusion We herein report novel cytogenetic abnormalities in patients with PCL (1 unique translocation involving chromosomes 6, 11 and 14 as well as 3 patients with t(1; 16) which has rarely been reported). Despite generally poor outcomes with traditional therapies, patients treated with novel agents and allogeneic transplant may enjoy a longer survival than previously reported. Disclosures Off Label Use: Lenalidomide in newly diagnosed myeloma. Baz:celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Real World Data In Myeloma: Experiences From The Swedish Population-Based Registry On 2494 Myeloma Patients Diagnosed 2008-2011

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1972-1972 ◽  
Author(s):  
Cecilie Blimark ◽  
Erik Holmberg ◽  
Gunnar Juliusson ◽  
Hareth Nahi ◽  
Forsberg Karin ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Real World ◽  
Clinical Intervention ◽  
Population Based ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia ◽  
First Report ◽  
One Year ◽  
The Impact

Abstract Introduction The Swedish Myeloma Registry (SMR) is a prospective observational registry designed to document real-world management and outcomes in newly diagnosed myeloma, with the purpose to improve the quality of the management of patients in Sweden. Population-based registries may provide complementary information on the management of patients to that of clinical intervention trials. With high representation and excellent data quality we can present valuable information in a whole population and reduce the impact of selection on outcome and reduce the subsequent problem with extrapolating data from clinical intervention studies on non-study populations. Methods The registry comprises web-reported data on all patients diagnosed with myeloma, plasmocytoma, and plasma cell leukemia from 2008 in Sweden, at time of diagnosis and after one year of follow-up. Coverage is analyzed through the compulsory Swedish Cancer Registry. Survival is achieved from the Swedish Tax Agency. Missing data are actively requested. This first report contains data on patients diagnosed between 2008 and 2011 with follow-up after one year on patients with symptomatic disease 2008-2010, with a follow-up through the end of 2012. Analyses of incidence, patient characteristics at baseline, proportion of patients given intensive treatment, obtaining very good partial remission (VGPR) and overall survival (OS) were estimated. Results Clinical data at baseline was available for 2494 patients (96% coverage)and 1- year follow-up data on 1427 patients (90% of all symptomatic cases initially reported), from 70 different centers in Sweden. The age adjusted incidence was 6.5 myeloma cases per 100 000 inhabitants and year. The median age was 70 years for men, and 73 years for women (34% younger than 66 years). At diagnosis, 76% were reported as symptomatic myeloma, 18% as smouldering myeloma, 5% plasmocytoma and 1% plasma cell leukemia. IgG-myeloma was most common (59%), followed by IgA (21%), Bence-Jones (13%), non-secretory (4%), IgD and IgM both less than 1%. Among symptomatic myeloma (n=1910), 76% had osteolytic lesions or compression fractures at diagnosis. Anemia (defined as hemoglobin levels below 10 g/dl) was seen in 33%, impaired kidney function (s-creatinin levels above 173 mmol/l) in 18%, and hypercalcemia in 21% at the time of diagnosis. In patients were ISS was available, 23%, 45% and 32% were in stage I, II, and III, respectively. Previous MGUS was known in 13 % of patients. Overall, 81 % of patients 65 years or younger received autologous stem cell transplantation (ASCT) and 4% of the elderly population. In the patients aged 65 years and younger, 63% of patients received one of the newer drugs in the first year of treatment, for the patients 66 to 80 years the number was 56%, and 25% of patients above 80 years. Throughout the study period, an increase in VGPR-rate on initial treatment was observed, more pronounced in younger patients (<66 years), from 35% in 2008 to 46% in 2010. For patients >65 years, the VGPR-rate increased from 17 to 27%. After a median of follow-up time of three years, OS was 63%. There was a significant difference in absolute and relative survival between younger and older patients. In symptomatic myeloma, patients 65 years or younger had an expected 3-year survival of 76% and in patients 66 years and above it was 50% (Figure). The relative 3-year survival for patients with asymptomatic patients was 81%. Discussion SMR is an instrument for increased quality in the management of plasma cell neoplasms in Sweden. This first report from the registry shows very high coverage and good adherence to guidelines in all regions of Sweden, both in diagnostics and treatment. A great effort is made to make the SMR complete and to present population-based data on management and outcome in Sweden. Longer follow-up is needed to address the question of the impact of new treatment options on the survival. The registry gives a great opportunity to perform population-based research of high quality based on the acceptance of the registry among treating physicians. Disclosures: Turesson: Celgene Corp: Honoraria.

Plasma Cell Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. SCI-4-SCI-4
Author(s):  
Rafael Fonseca
Keyword(s):  
Plasma Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Plasma Cell Leukemia ◽  
Induction Treatment ◽  
Cell Transplant ◽  
Cell Leukemia ◽  
Initial Manifestation ◽  
Durable Response ◽  
The Impact

Abstract Abstract SCI-4 Introduction Plasma cell leukemia (PCL) represents an aggressive variant of multiple myeloma (MM) characterized by the presence of large number of circulating plasma cells (PC) in the peripheral blood. While some boundaries have been defined to establish a diagnosis of PCL (PC in the peripheral blood greater than 2×109/l-1 or 20% of leukocytes being plasma cells), these values are artificial, and most cases of PCL show extreme numbers of circulating plasma cells. PCL is part of a spectrum of the PC neoplasms where increasing numbers of circulating PC identify aggressive MM, yet many cases do not satisfy criteria for PCL. Historically PLC has been divided into “Primary PCL” (pPCL) when it represents the initial manifestation of a PC neoplasm, and “Secondary PCL”, or MM with leukemic transformation (MM-LT). Both entities share biologic and clinical similarities as aggressive variants of MM, but the latter represents a fulminant PC neoplasm with historic survival of only 1-2 months. In contrast, pPCL, while nevertheless aggressive, often will respond to induction treatment and can occasionally result in a durable response. Biology Because of the rarity of PCL (1% or less of all MM) the genetic description of the disease has been limited by lack of material for study. Nevertheless most PCL cases harbor IgH translocations (87% of pPCL and 82% in MM-LT). In particularly the t(11;14)(q13;q32) is common; observed in 35 to 70% of cases of pPCL. In contrast MM-LT contains most other genetic aberrations associated with MM pathogenesis, including the more benign genetic variants of the disease (e.g. hyperdiploid MM), and these cells are presumed to have acquired additional genetic features resulting in aggressive clonal proliferation and expansion. When karyotypes are informative (frequently in PCL) they are almost always non-hyperdiploid variant, mostly hypodiploid. Rare cases of hyperdiploid karyotypes have been observed in association with MM-LT. Monoallelic deletions of 17p13.1, at the TP53 locus and similar to those seen in MM, can be detected in 50% of pPCL and 75% of MM-LT. While mutations of TP53 area rare in MM they are common in PCL (24%), contributing to a substantial overall prevalence of TP53 inactivation of 56% in pPCL and 83% in MM-LT. Furthermore, we found the upstream tumor suppressor p14ARF, whose product directly binds MDM2 enhancing p53 function, to be inactivated by methylation in 29% of MM-LT. MYC abnormalities are only observed in 15% of cases and the distribution of chromosome 13 deletion/monosomy is similar to what would be expected for the corresponding karyotypic aberrations (85% in the hypodiploid pPCL and 50% in MM-LT). Treatment and future directions Historically the treatment of PCL has been unsatisfactory with few patients achieving durable remissions, and most dying within weeks to months after diagnosis. The impact of more intensive regimens (including autologous and allogeneic stem cell transplant) and of novel agents such as bortezomib and lenalidomide are not known. However, early data suggest, that the historic survival rates of pPCL (∼12 months) and MM-LT (∼1-2 months) will be improved by the aforementioned interventions. It is likely that with increasing survival of MM patients, MM-LT will become an increasingly common and difficult problem to manage. Disclosures Fonseca: Various: CME lectures; Halozyme: Consultancy; BMS: Consultancy; Medtronic: Consultancy; AMGEN: Consultancy. Off Label Use: Multiple agents to be used for the treatment of plasma cell leukemia. No agents are specifically approved for this indication although this is a variant of myeloma.

Has the Prognostic of Primary Plasma Cell Leukemia Improved with New drugs?

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3869-3869 ◽  
Author(s):  
Driss Chaoui ◽  
Xavier Leleu ◽  
Murielle Roussel ◽  
Bruno Royer ◽  
Marie-therese Rubio ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Plasma Cell Leukemia ◽  
Novel Agents ◽  
Haematopoietic Stem Cell ◽  
High Dose ◽  
Cell Leukemia ◽  
Overall Response ◽  
The Impact

Abstract Abstract 3869 Poster Board III-805 Introduction The outcome of patients with plasma-cell leukemia (PCL) is poor. Avet-Loiseau reported on behalf the IFM, our first experience in PCL patients and showed that the median overall survival (OS) was 8 months (Avet-Loiseau, Blood, 2001). Since 1999, novel agents such as Thalidomide, Bortezomib (Velcade) or Lenalidomide (Revlimid) have been widely used in the treatment of multiple myeloma, both at the time of relapse or part of upfront therapy. Patients and methods In this retrospective analysis, we have looked at the outcome of PCL patients treated within the IFM since 1999 in order to study the impact of novel agents on survival. Results 31 cases, 20 males, 11 females, median age 55 years (34-78) were analyzed. Twenty one patients less than 65 years received high-dose therapy as part of frontline treatment : 19 autologous haematopoietic stem cell transplantation (HSCT) and 5 allogeneic transplantation. Novel agents were used part of induction therapy in 6 cases, at the time of relapse for 9 patients, for both induction and relapse in 16 cases. Thirteen patients received 1 novel agent, 11 received 2 and 7 patients received the 3 novel agents. The median number of lines of therapy was 2 (1 to 4). Bortezomib was used as up front treatment in 15 patients and at relapse for 9 patients. Overall response rate according the IMWG criterias was 70% (17/24) including 11 CR or VGPR (45%). PAD (Bortezomib, Adriamycin and Dexamethasone) and VTD (Bortezomib, Thalidomide, Dexamethasone) regimens provided the best response rates. Lenalidomide was used in 13 patients mostly at relapse. A response was obtained in 53% of patients including 2CR and 2 VGPR (30%). Nineteen patients were treated with Thalidomide-based regimens. Overall response rate was 52% (10/19) including 2 CR and 6 VGPR (31%). Overall, for the whole group of patients, the median progression-free survival was 8 months (0-26) and the median OS was 15 months (6-108). When comparing this survival with that described in our previous experience reported before 1999, we clearly showed that the use of novel agents improved the survival of patients with PCL. Conclusion In this retrospective study, novel agents improved the prognosis of P-PCL. Prospective IFM phase II studies are ongoing to confirm these results. Disclosures: No relevant conflicts of interest to declare.

Primary Plasma Cell Leukemia Has a Poor Prognosis Even in the Era of Novel Agents - a Multicenter Case Series

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5699-5699
Author(s):  
Chezi Ganzel ◽  
Ory Rouvio ◽  
Hila Magen ◽  
Osnat Jarchowsky ◽  
Irit Avivi ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Plasma Cells ◽  
Case Series ◽  
Plasma Cell Leukemia ◽  
Novel Agents ◽  
Cell Leukemia ◽  
Medical Centers ◽  
Disease Characteristics ◽  
Light Chain Disease ◽  
Primary Plasma Cell Leukemia

Abstract Introduction: Primary plasma cell leukemia (PPCL) is a rare and aggressive variant of multiple myeloma (MM), characterized by the presence of 20% and/or 2X109/L plasma cells (PCs) in the peripheral blood (PB) of the patient. Data regarding this entity are scarce and based on case reports and few retrospective case series. Most of the reports are dated prior to the incorporation of novel agents into MM treatment. The aim of this multicenter retrospective study was to evaluate the response and survival of PPCL patients in the era of the novel agents. Methods: We searched for the diagnosis of PPCL, during the years 2002-2016, in the medical summaries of 16 medical centers in Israel which routinely treat patients with MM. Patients with the presence of plasma cells in the blood during the course of MM (secondary plasma cell leukemia) were excluded. Results: 40 PPCL patients were identified in 11 of the 16 medical centers. It is probable that several patients were recorded as MM and thus not identified as PPCL. The characteristics of the patients and their disease are available for 35 patients and are summarized in table 1. One third of the patients presented with light chain disease and over two thirds had hypercalcemia at diagnosis. The median age was 60 and 3 patients were aged less than 35 years at diagnosis. The median number of treatments was 2. 83% of the patients received at least one IMiD or proteosome inhibitor (PI), 51% received both IMiD and PI. 17% of the patients received more than one line of IMiDs and a similar number of patients received more than one line of PIs (Fig. 1). The type of novel agents that were used are shown in figure 2. 45.7% of the patients underwent hematopoietic stem cell transplant (HSCT), of those, 4 patients (11%) have undergone tandem auto-allo HSCT and 1 (3%) - tandem auto-auto HSCT. 29% of the patients did not responded to induction therapy and 57% achieved PR or better response. 13 out of 35 patients (37%) are still alive and one is lost to follow-up. The median overall survival (OS) was 11 months.7 patients (20%) survived less than 2 months while 13 (37%) survived more than 24 months, including 7 who survived more than 48 months. Among the 16 patients who underwent HSCT, all the 4 who underwent tandem auto-allo-transplant survived more than 32 months. Conclusions: Despite the modest size of this patient cohort, several inferences may be made. Patients with PPCL have unique characteristics compared to MM patients; lower median age, more frequent light chain disease and hypercalcemia at presentation. Extreme leukocytosis or leukopenia are rare. Despite intensive use of novel agents, the median OS of this cohort remains poor - 11 months. The best results were seen in patients who received tandem auto-allo HSCT, suggesting that the immunotherapeutic graft-versus-myeloma effect may offer the best hope for long-term survival to patients with PPCL. Table 1 Patient and disease characteristics Table 1. Patient and disease characteristics Figure 1 Combinations of novel agents Figure 1. Combinations of novel agents Figure 2 Types of novel agents Figure 2. Types of novel agents Disclosures Avivi: Tel Aviv Sourasky Medical center: Consultancy, Other: consultancy to :BMS Roche.

Plasma Cell Leukemia: A Report on Three Patients

1983 ◽  
Vol 69 (6) ◽  
pp. 589-591 ◽  
Author(s):  
Leonardo Pacilli ◽  
Paolo Ferraro ◽  
Silvia Cochi ◽  
Antonio De Laurenzi
Keyword(s):  
Plasma Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Periodic Acid ◽  
Previous History ◽  
Bone Marrow Aspiration ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia ◽  
Periodic Acid Schiff ◽  
The Third

Three patients with plasma cell leukemia are reported. Two of them had a previous history of myeloma; the third one started with a plasma cell leukemia. Diagnosis was made from the required presence of 20% plasma cells in the peripheral blood. In all 3 cases, bone marrow aspiration and peripheral blood showed plasma cells strongly positive for acid phosphatase and alpha-naphthyl acetate esterase, and negative for periodic acid-Schiff. The first patient was treated with a polychemotherapy regimen that included vincristine, cyclophosphamide, chlorambucil and prednisone, and the second patient with melphalan and prednisone; the third one, who started with plasma cell leukemia, received total body irradiation at the dose of 600 rad. The results of the therapy and survival time, which was never more than 3 months, are in accord with other reports in the literature.

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

A Pilot Study of Lenalidomide and Dexamethasone as First Line Therapy in Patients with Primary Plasma Cell Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4951-4951
Author(s):  
Pellegrino Musto ◽  
Maria Teresa Petrucci ◽  
Fortunato Morabito ◽  
Francesco Nobile ◽  
Fiorella D'Auria ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Early Response ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Primary Plasma Cell Leukemia

Abstract Abstract 4951 Background Primary Plasma Cell Leukemia (PPCL) is an aggressive, rare variant of multiple myeloma, with clinical, molecular and phenotypic peculiarities, which accounts approximately for 2% to 4% of all myeloma diagnoses. The prognosis of PPCL patients is usually poor, with less than half of patients responding to conventional chemotherapy and a median survival of 7 months. Even by using autologous or allogeneic transplant procedures, survival generally does not exceed three years. Bortezomib has recently provided some promising results in this setting, but, given all the above, new treatments for PPCL are greatly awaited. Lenalidomide is a new immunomodulating agent with great efficacy in multiple myeloma, especially when associated with dexamethasone or other drugs. There are, indeed, some sporadic case reports of PPCL patients treated with lenalidomide as salvage therapy, but no data are currently available on the use of this drug as first line therapy in this disease. Patients and Methods On March, 2009, we started an open label, prospective, multicenter, exploratory, single arm, two-stage study aiming to evaluate safety and antitumor activity of the lenalidomide/low dose dexamethasone combination (Rd), as first line therapy in patients with PPCL. The primary endpoint was early response rate according to International Uniform Criteria. The secondary endpoints were TTP, PFS, OS, percentage of eligible PPCL patients able to collect peripheral blood stem cells and to undergo autologous or allogeneic stem cells transplantation after Rd, serious and severe adverse event rate. According to this study protocol, all eligible, newly diagnosed adult patients with PPCL receive Lenalidomide at a dose of 25 mg daily for 21 days every 28 days. Oral dexamethasone is administered at a dose of 40 mg daily on days 1, 8, 15, and 22 for each 28-day cycle. After 4 cycles, patients who achieve at least PR and not eligible for autologous or allogeneic stem cell transplantation, continue with Rd until clinically appropriate (disease progression, unacceptable toxicity, patient's decision to leave the protocol). In these patients, a maintenance dose of lenalidomide alone equal to 10 mg/die days 1-21 every month is considered after at least 8 full dose Rd cycles. Patients responding after 4 Rd cycles and eligible for transplant procedures, proceed according to single Centre transplant policy. Patients not responding after 4 cycles or progressing under Rd treatment are considered off-study. Appropriate contraception methods and anti-thrombotic prophylaxis are planned. Results Four enrolled patients (1 male, 3 female, mean age 65 years, range 58-69) are currently evaluable for early response. All had unfavourable cytogenetics, including del13, t(4;14), t (14;16), or a complex karyotype. Circulating plasma cells ranged from 4.4 to 9.2 ×10e9/l. One patient had at baseline a moderate degree of renal failure (serum creatinine levels 2 mg/dl). After at least 2 Rd cycles (range 2-4), two PR and two VGPR were achieved (overall response rate 100%), with disappearance or near complete reduction of circulating plasma cells in all cases. The most relevant toxicities were grade 3 neutropenia and pneumonia, occurring in one patient and resolved by appropriate lenalidomide dose reduction, introduction of G-CSF and antibiotic therapy. One patient died in PR, due to causes unrelated to PPCL or treatment. As, according to the Simon, two-stage design adopted, more than two responses occurred within the first ten patients enrolled (stage 1), a total of 22 PPCL subjects will be accrued to complete the stage 2 of the trial. Conclusions These findings, though very preliminary, suggest that the combination of lenalidomide and dexamethasone may be a safe and promising initial therapy for PPCL patients, which can rapidly control the disease and could permit to perform following single patient-adapted therapeutic strategies. An update of this study, including molecular data, a larger number of patients and a longer follow-up, will be presented at the Meeting. Disclosures Musto: Janssen-Cilag: Honoraria; Celgene: Honoraria, Research Funding. Off Label Use: Lenalidomide is approved in Italy for advanced multiple myeloma, not for plasma cell leukemia. This is a clinical trial registered at AIFA (Italian regulatory Agency for Drugs), EudraCT No. 2008-003246 28. Petrucci:Janssen-Cilag: Honoraria; Celgene: Honoraria. Morabito:Celgene: Honoraria; Janssen-Cilag: Honoraria. Cavo:Celgene: Honoraria; Janssen-Cilag: Honoraria. Boccadoro:Celgene: Honoraria; Janssen-Cilag: Honoraria. Palumbo:Celgene: Honoraria; Janssen-Cilag: Honoraria.

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.

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