Outcomes of patients with primary plasma cell leukemia (pPCL) in the era of novel agent therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20510-e20510
Author(s):  
Bharat Nayar Nandakumar ◽  
Shaji Kumar ◽  
Angela Dispenzieri ◽  
Francis Buadi ◽  
David Dingli ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Plasma Cell ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
Stem Cell Transplant ◽  
Plasma Cells ◽  
Rank Test ◽  
Cell Transplant ◽  
Novel Agent

e20510 Background: pPCL is a rare and aggressive form of multiple myeloma (MM) with dismal survival outcomes compared to the remainder of MM patients. Several studies have validated the optimal cutoff for defining pPCL to be >5% circulating plasma cells (cPCs) on a peripheral blood smear due to equally poor outcomes in this less restrictive cohort. We evaluated the clinical outcomes and cytogenetic features of patients diagnosed with pPCL at our institution that were treated with novel agent induction therapies. Methods: We evaluated patients with pPCL diagnosed between 2000 – 2018 (using the 5% cut off) at Mayo Clinic, Minnesota. Data was extracted from a prospectively maintained database and from the review of electronic medical records. Patients were categorized as having high risk (HR) cytogenetics if any of the following abnormalities were present: del 17p, t(4;14), t(14;16) or t(14;20). Chi-square tests and Fisher exact tests were used to compare differences between sub-groups. Survival analysis was performed by the Kaplan-Meier method and differences assessed using the log rank test. Results: This cohort consisted of 67 patients with pPCL with a median age of 62 years (range: 34-91) of which 33 (46%) were male. The median follow up was 46 months (95% CI: 41 – 90). The median bone marrow plasma cell involvement was 84% (Range: 10 – 100) and the median cPCs percentage on the peripheral blood was 23% (range: 5 - 93). Data on primary cytogenetic abnormalities were available in 60 (85%) patients and the distribution was as follows: t(11;14) – 27 (45%), t(4;14) – 5 (8%), t(14;16) – 8 (13%), t(14;20)- 3(5%) and del 17p- 15(25%). All patients received novel agent induction therapy with 36 (54%) having received autologous stem cell transplant and 4 undergoing an allogeneic stem cell transplant. The median time to next therapy (TTNT) and overall survival (OS) for all patients was 13 months (95% CI: 9 – 17) and 24 months (95% CI: 19 – 40) respectively; 16 months and 51 months for standard risk (SR) vs. 10 months and 19 months for HR (P = 0.005 for OS), when stratified by cytogenetic risk. There were only 17 (31%) patients who were alive for ≥48 months since diagnosis (i.e. twice the median OS of this cohort); The absence of high risk cytogenetics (P = 0.049) and non-elevated LDH level (P = 0.047) at diagnosis predicted for achieving this survival goal. Conclusions: The outcomes of patients diagnosed with pPCL remain poor despite the use of novel agent induction therapy. However, some patients appear to do better than expected and this phenomenon may be influenced by the presence of HR cytogenetics.

Stem Cell Transplant in Multiple Myeloma: Impact of Response Failure in the Era of Novel Therapies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1878-1878
Author(s):  
Morie A Gertz ◽  
Shaji Kumar ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
David Dingli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Novel Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Novel Agent

Abstract Abstract 1878 Poster Board I-900 Autologous stem cell transplant as a platform for multiple myeloma treatment is the standard of care for patients who can safely withstand the procedure. Before novel agents were introduced, one-third to one-half of patients did not achieve partial response at transplant. Previously published medical literature has showed that in this past era, absence of initial response to induction therapy had no impact on progression-free survival and overall survival after high-dose therapy. Lack of response to initial induction did not preclude a good response after stem cell transplant. With the introduction of novel agents—immunomodulatory drugs and proteasome inhibitors—response rates with initial therapy are now between 70% and 100%. This retrospective study analyzes progression-free survival and overall survival in patients who do not have a partial response after induction therapy with a regimen that contains a novel agent. Unlike patients in reports published previously—before novel agents—patients who do not achieve partial remission have a significantly shorter overall survival from transplant (74.0 vs 43.5 months) and a shorter progression-free survival (22.6 vs 13.1 months; P<.001). Absence of a response to induction therapy with a novel agent predicts a poorer outcome after high-dose therapy.{abstabft}.b CR+VGPR for plateau, P<.001 compared with other 3 categories. Failure to respond to novel-agent induction leads to shorter posttransplant progression-free survival (PFS). Failure to respond to novel-agent induction leads to shorter posttransplant overall survivalDisclosures: Gertz: celgene: Honoraria; millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Kumar: celgene: Honoraria; millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Lacy: celgene: Honoraria; millenium: Honoraria.TableMultivariable Analysis of Posttransplant Progression-Free SurvivalVariableP ValuePlateau vs relapsed-refractory.003Albumin.86Sex.94b2-Microglobulin.89Bone marrow plasma cells.18Age.75Abnormal cytogenetics.002CTX mobilization.51Labeling index.002

scholarly journals Late effects in survivors of tandem peripheral blood stem cell transplant for high-risk neuroblastoma

2008 ◽  
Vol 51 (5) ◽  
pp. 679-683 ◽  
Author(s):  
Wendy L. Hobbie ◽  
Thomas Moshang ◽  
Claire A. Carlson ◽  
Elizabeth Goldmuntz ◽  
Nancy Sacks ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Late Effects ◽  
Peripheral Blood ◽  
Stem Cell Transplant ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
Cell Transplant

scholarly journals Clinical Outcomes and Cytogenetic Features of Primary Plasma Cell Leukemia (pPCL) in the Era of Novel Agent Induction Therapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5490-5490
Author(s):  
Bharat Nandakumar ◽  
Shaji K. Kumar ◽  
Francis K. Buadi ◽  
Angela Dispenzieri ◽  
David Dingli ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Plasma Cell ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
Research Funding ◽  
Blood Smear ◽  
Peripheral Blood Smear ◽  
Advisory Committees ◽  
Novel Agent

BACKGROUND: pPCL is a rare and aggressive form of multiple myeloma (MM) with poor survival outcomes compared to that experienced by MM patients. It has been traditionally defined by the presence of an absolute plasma cell count of > 2000/microL or >20% circulating plasma cells (cPCs) in the peripheral blood. However, several recent studies have validated the optimal cutoff for defining pPCL to be >5% cPCs on a peripheral blood smear due to equally poor outcomes in this less restrictive cohort. Hence, given the rarity of this disease entity, we evaluated the clinical outcomes and cytogenetic features of patients diagnosed with pPCL at our institution with the new proposed definition of pPCL by >5% cPCs on peripheral blood smear that were treated with novel agent induction therapies. METHODS: We evaluated all patients with pPCL diagnosed between 2000 - 2018 evaluated at Mayo Clinic in Rochester, Minnesota. Data regarding these patients were extracted from a prospectively maintained database and from the review of the electronic medical records. Patients were categorized as having high risk cytogenetics if any of the following abnormalities were present: del 17p, t(4;14), t(14;16) or t(14;20). Chi-square tests and Fisher exact tests were used to compare differences between the sub-groups of interest. Survival analysis was performed by the Kaplan-Meier method and differences assessed using the log rank test. RESULTS: This cohort consisted of 71 patients with pPCL with a median age of 62 years (range: 34-91) of which 33 (46%) were male. The median follow up was 46 months (95% CI: 41 - 90). The median bone marrow plasma cell content was 84% (Range: 10 - 100) and the median plasma cell percentage on the peripheral smear was 23% (range: 5 - 93). There were 48 (68%) patients with >20% cPCs in their peripheral blood smear. Only 23 (32%) patients had concurrent information on the number of cPCs by multiparametric flow cytometry at diagnosis and the median number of cPCs detected was 32,807 per 150,000 events analyzed (Range: 354 - 132,256). There were 15/54 (28%) patients who presented with a creatinine of 2 mg/dL or greater and 17/55 (31%) pts who presented with hypercalcemia (11 mg/dL or greater). Data for ISS classification was available in 45 patients and is as follows: Stage 1- 3 (7%) patients, Stage 2- 10 (22%) patients and Stage 3- 32 (71%) patients. Data on the presence of primary cytogenetic abnormalities were available in 60 (85%) patients of which 29 (49%) had high risk cytogenetics. The distribution of primary cytogenetic abnormalities among this cohort was as follows: t(11;14) - 27 (45%), t(4;14) - 5 (8%), t(14;16) - 8 (13%), t(14;20)- 3(5%) and del 17p- 15(25%). All patients received novel agent induction therapy with 40 (57%) of them having received at least one autologous stem cell transplant and 1 patient undergoing an allogeneic stem cell transplant. The median overall survival (OS) for all pPCL patients in this cohort was 23 months (95% CI: 19 - 38). The OS was similar in patient with 5-19% cPCs vs. >20% cPCs (24 vs. 23 months, P = 0.999). However, when the entire cohort was stratified by cytogenetic risk, the median OS was 51 months for standard risk vs. 19 months for high risk (P = 0.005) (FIGURE). There were only 17 (30%) patients in this cohort who were alive for 48 months or longer since diagnosis (i.e. twice the median OS of this cohort) and they were more likely to not have high risk cytogenetics at diagnosis (P = 0.05). CONCLUSION: In this analysis of one of the largest contemporary cohorts of pPCL patients, the outcomes of patients diagnosed with pPCL remain poor despite the use of novel agent induction therapy. However, some patients appear to do better than expected and this phenomenon may be influenced by the absence of high risk cytogenetics. Disclosures Kumar: Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Dispenzieri:Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Dingli:Karyopharm: Research Funding; Rigel: Consultancy; Millenium: Consultancy; Janssen: Consultancy; alexion: Consultancy. Lacy:Celgene: Research Funding. Kapoor:Glaxo Smith Kline: Research Funding; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Cellectar: Consultancy; Celgene: Honoraria; Janssen: Research Funding. Russell:Imanis: Equity Ownership. Leung:Omeros: Research Funding; Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees. Gertz:Celgene: Consultancy; Prothena Biosciences Inc: Consultancy; Appellis: Consultancy; Amgen: Consultancy; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding; Janssen: Consultancy; Ionis/Akcea: Consultancy; Alnylam: Consultancy; Annexon: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Research to Practice: Consultancy; Teva: Speakers Bureau; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Spectrum: Consultancy, Research Funding; i3Health: Other: Development of educational programs and materials; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau.

scholarly journals Optimizing Autologous Stem Cell Transplant for High-Risk Patients with Plasma Cell Dyscrasias

2018 ◽  
Vol 24 (3) ◽  
pp. S135
Author(s):  
Ehsan Malek ◽  
Gina Hoffman ◽  
Richard Creger ◽  
Brenda Cooper ◽  
Merle Kolk ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Plasma Cell ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
High Risk Patients ◽  
Risk Patients ◽  
Plasma Cell Dyscrasias

Increased Calreticulin Expression in Clonal Plasma Cells Is Associated with Complete Response to Melphalan and Autologous Stem Cell Transplant in Systemic Light-Chain Amyloidosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3096-3096 ◽  
Author(s):  
Ping Zhou ◽  
Adam B. Olshen ◽  
Julie Teruya-Feldstein ◽  
Raymond Comenzo
Keyword(s):  
Stem Cell ◽  
Plasma Cell ◽  
Light Chain ◽  
Stem Cell Transplant ◽  
Plasma Cells ◽  
Complete Response ◽  
Trna Synthetase ◽  
Cell Transplant ◽  
Cell Disease ◽  
Light Chain Amyloidosis

Abstract Systemic light-chain amyloidosis (AL) is a protein deposition disorder and a monoclonal plasma cell disease. Treatment of AL has focused on the reduction or elimination of the clonal plasma cells that make amyloid-forming light chains. High-dose melphalan and stem cell transplant (MEL SCT) is an effective therapy for selected AL patients. At 3 months post-SCT, response of the clonal plasma cell disease can be reliably scored; the achievement of a complete response (CR= immunofixation negative) is usually associated with extended survival while no response (NR= < 50% reduction) is not. Many factors likely contribute to this distribution of responses. In order to identify factors specific to clonal plasma cells, gene expression profiles (GEP; Affymetrix U133 PLUS 2.0) were obtained using FACS-sorted CD138+/DAPI- plasma cells (>95% pure) from untreated AL patients before SCT. Supervised analyses were then performed based on responses at 3 months post-SCT, comparing the CR (n=4) and NR (n=5) groups. The basic analysis was a t-test, filtering genes for differential expression at p<0.01, and those that passed were subject to EASE analysis in order to identify gene ontology families over-represented on the gene list. A secondary filtering selected only genes with two-fold difference in expression between CR and NR, average expression of at least 1000, and inclusion in an EASE group that had a p<0.05. Five genes were identified as over-expressed in the CR group: WARS, SHMT2, IARS, CALR, and PSMB4. Our initial validation studies, using purified baseline clonal plasma cells from 11 patients and baseline marrow biopsy specimens from 25 patients, have focused on calreticulin (CALR) and tryptophanyl tRNA synthetase (WARS). By real-time polymerase chain reaction studies with GAPDH and normal plasma cell controls, the expression levels of CALR were significantly lower in NR patients (p=0.02) while differences in WARS expression did not achieve significance (p=0.25). By immunohistochemical (IHC) staining for CALR in marrow biopsies, a CALR IHC index was developed, with scoring of the fraction of plasma cells expressing CALR (over total CD138 positivity) and intensity of CALR staining (both scored 0, 1, 2 or 3; the scores were multiplied to compute the index, range 0–9). CALR-stained marrows were scored blindly. Patients with CALR index of 9 had an 88% likelihood of achieving CR while those with scores of 0–6 had a 39% chance (Fisher’s exact test, p=0.046). In sum, calreticulin expression in clonal plasma cells from AL patients is associated with the response to MEL SCT. Further studies are on-going to determine the basis for this association.

Time until Transfusion Independence in Haplo-Cord Transplant Is Comparable to Matched Unrelated Stem Cell Transplant, a Single Institution Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4331-4331
Author(s):  
Hamilton C. Tsang ◽  
Lohith S. Bachegowda ◽  
Ruchika Goel ◽  
Nebu V. Koshy ◽  
Usama Gergis ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplant ◽  
Disease Risk ◽  
Rank Test ◽  
Mortality Data ◽  
Cell Transplant ◽  
Transfusion Independence ◽  
Transfusion Requirements ◽  
Significant Difference

Abstract Introduction: Stem cell transplant (SCT) is a curative therapy for several advanced hematologic malignancies. In the peri-transplant period, red blood cell (RBC) and platelet (PLT) transfusions are often necessary until engraftment. Time until transfusion independence (TI) is influenced mainly by time to engraftment. Haplo-cord (HC) transplant combines an umbilical cord blood unit graft with a CD34 selected adult haplo-identical graft for the purpose of establishing long term cord engraftment. No prior studies have compared TI between HLA matched related donors (MRD), unrelated donors (MUD) and HC allotransplant recipients. Methods: Patient demographics, ASBMT disease risk classification, relapse and mortality data for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) patients undergoing MRD, MUD, and HC SCT between 1/2012-1/2015 were included. Time until TI for RBC and PLT was defined as the day of the last transfusion with no transfusions in the following 30 days (d). The cohorts were followed for 180d post-transplant. Kaplan-Meier survival method was used to compare time until RBC and PLT transfusion independence between different transplant types and ASBMT risk categories. Data were censored on disease relapse or death. Log-rank test was used to compare the survival probabilities. Statistical analyses were performed using SAS 9.4.0 (SAS Institute, Cary, NC). Results: A total of 194 AML/MDS patients received MRD (n=63, 32%), MUD (n=76, 39%), and HC (n=55, 28%) SCT. TI was achieved for RBC transfusion in 84%, 74%, and 67% of patients, and for PLT transfusion in 84%, 91%, and 85% of patients for MRD, MUD, and HC respectively. The time to attain RBC and PLT TI was not statistically different between HC and MUD transplants (log-rank p=0.16 and 0.09 respectively) (Fig. 1: A, C). Within the ASBMT high risk strata, no statistical differences in the time to attain RBC (log-rank p=0.15) and PLT (log-rank p=0.55) TI between any transplant types could be detected (Fig. 1: B, D). Conclusion: Recipients of SCT often have substantial transfusion requirements. No statistically significant difference in time to TI was seen between HC and MUD recipients. No statistically significant differences in time to TI were seen between HC, MUD and MRD recipients in the ASBMT high risk strata. Time until transfusion independence in haplo-cord transplant is comparable to matched unrelated stem cell transplant. Figure 1. Figure 1. Disclosures van Besien: Miltenyi Biotec: Research Funding.

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