ID:2035 Chromosomal abnormalities and treatment response in Multiple myeloma patients at Cho Ray hospital

Multiple myeloma (MM) is a malignant plasma cell, generating abnormal immunoglobulins in the blood and urin. From January 2012 to December 2014, we performed chromosome analysis and treatment for 44 MM patients with the regimens containing Bortezomib (VD, VMP, VD plus autologus hematopoietic stem cell transplantation) at the Hematology department, Cho Ray hospital. The patient median of age was 64 year old, with the proportion of male/female was 0.83. IgG and IgA were two most common M-protein with accounting for 44.7% and 22.7%, respectively. Patients were usually admitted to the hospital late in phase II and III of disease. 43 of 44 MM patient haboring chromosomal abnormalities. Karyotyping analysis results showed that 3.7% cases with hypodiploidy and 14.8% cases hyperdiploidy. Translocation t(4;14), t(6;14), t(11;14) and t(14;16) were found in 6.8%, 4.5%, 11.3% and 4.5% of cases, respectively. Del(13q) and del(17p) accounted for 31.8% and 29.5% of cases. High risk group was found in 40.9% of cases. Patients carrying the translocation t(4;14) had the worse prognosis than other abnormalities with low response rate and overall survival, whereas higher rate of mortality. Results of our study showed that chromosomal abnormalities in MM are diversity and high percentage that affect the prognosis. Therefore, we need to indentify chromosomal abnormalities before treatment to select appropriate therapy regiments.

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PROGNOSIS IN NEWBORN INFANTS WITH X-CHROMOSOMAL ABNORMALITIES

PEDIATRICS ◽

10.1542/peds.47.4.681 ◽

1971 ◽

Vol 47 (4) ◽

pp. 681-688

Author(s):

Eleanor Eller ◽

William Frankenburg ◽

Mary Puck ◽

Arthur Robinson

Keyword(s):

Home Environment ◽

Chromosomal Abnormalities ◽

Newborn Infants ◽

Evaluation Process ◽

Chromosome Analysis ◽

Pedigree Analysis ◽

High Risk Group ◽

The Past ◽

Normal Limits ◽

Growth Abnormalities

Sex-chromosomal aberrations occur with a relatively high frequency and have been associated with mental retardation, perceptual problems, psychopathology, and growth abnormalities. Identification of this possibly high risk group at birth enables the study of their growth and development to determine if and when they deviate from normal. Routine screening of the chromatin constitution of 21,214 consecutive newborn infants has identified 32 babies with gross X chromosome abnormalities. Three died in the newborn period. During the past 5 years, 27 children have been followed from birth. The evaluation process consists of semiannual and annual physical and developmental examinations, psychological testing, growth measurements, pedigree analysis, dermatoglyphic analysis, home environment evaluation, and, in mosaics, repeated chromosome analysis. The patients with 45,X karyotypes have classical physical signs. The other patients have normal phenotypes, although several have minor physical manifestations such as clinodactyly and epicanthic folds. Overall development in all except two patients has been within normal limits. In mosaics, there is a tendency for the abnormal cell line to disappear.

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Durable Remission with Salvage Autotransplants in Patients with Multiple Myeloma.

Blood ◽

10.1182/blood.v114.22.1227.1227 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1227-1227

Author(s):

Nina Shah ◽

Khawaja Fraz Ahmed ◽

Sofia Qureshi ◽

Jatin Shah ◽

Robert Z Orlowski ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Median Time ◽

Chromosomal Abnormalities ◽

Retrospective Chart Review ◽

Progression Free Survival ◽

High Dose ◽

Hematopoietic Stem ◽

Remission Duration

Abstract Abstract 1227 Poster Board I-249 Background In comparison with single autologous hematopoietic stem cell transplantation (auto HCT), tandem autologous HCT has resulted in longer event-free and overall survival in randomized trials for patients with newly diagnosed multiple myeloma (MM). Most myeloma patients, however, only receive a single auto HCT. Many of these patients are eligible for a second auto HCT as salvage at the time of relapse. We evaluated the outcome of salvage auto HCT for MM patients treated at our institution. Methods We performed a retrospective chart review and identified 62 MM patients (38 males, 24 females) who received a second auto HCT as salvage between 1/3/1992 and 11/4/2008.. Preparative regimen was high-dose melphalan alone or in combination with other chemotherapy agents, including busulfan, topotecan and bortezomib. Three patients received a combination of thiotepa, busulfan and cyclophosphamide. Results Median interval between the first and salvage auto HCT was 21 months (range 2-81). Median age at salvage HCT was 55 years (37-73) and median prior treatment regimens were 4 (range 2-16). Twelve patients had chromosomal abnormalities on conventional cytogenetic studies. Patients received a median CD34 cell dose of 4 ×106 / kg (range 2.3-11.2). Fourteen patients (22%) experienced grade 3 or higher toxicity after the salvage auto HCT. Two patients died within 100 days with a TRM of 3%. Median time to neutrophil engraftment was 10 days (8-38). Responses after salvage auto HCT were as follows: CR+ near CR 15%, PR 48%, with an overall response rate of 63%. Twenty-seven (44%) patients received post auto HCT maintenance therapy. Median follow-up from salvage HCT was 25 months. Kaplan-Meier estimates of median progression-free survival and overall survival (OS) were 15.5 and 43.3 months, respectively. Median time to progression after the first and salvage auto HCT was 20 and 12 months, respectively, with total remission duration of 32 months from two HCTs. Median OS from the time of diagnosis was 72 months, comparable to reported results with tandem auto HCT. At last follow up, 20 patients were alive and in remission. Conclusions In selected MM patients a second auto HCT for salvage therapy is well tolerated with acceptable toxicity. The combined remission duration and overall survival are comparable to outcomes with tandem autotransplants. Disclosures Qazilbash: Cephalon: Speakers Bureau.

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Coexistance of Multiple Myeloma and Myelodysplastic Syndrome or Lymphoid Diseases At Diagnosis: Evidence for Two Clonal and Independent Chromose Abnormalities

Blood ◽

10.1182/blood.v118.21.5063.5063 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5063-5063

Author(s):

Hossein Mossafa ◽

Sabine Defasque ◽

Christine Fourcade ◽

JeanPierre Hurst ◽

Bertrand Joly

Keyword(s):

Multiple Myeloma ◽

Plasma Cells ◽

Chromosomal Abnormalities ◽

Conflicts Of Interest ◽

Critical Role ◽

Chromosome 8 ◽

Trisomy 8 ◽

Hematopoietic Stem ◽

Monosomy 7 ◽

Trisomy 12

Abstract Abstract 5063 Introduction, We describe the simultaneous presentation of multiple myeloma (MM) and yeloproliferative disorders (MPD) or lymphoid diseases (LD) at diagnosis. Therapy-related myelodysplasia (tMDS) occurring during the course of MM is generally believed as a result from hematopoietic stem cell-toxic therapies, such as ionizing radiation and alkylating agent-based chemotherapies (melphalan, nitrosoureas).Patients and methods, We study a total of 342 patients (151 F, 191 M; median age 68.1 years; range 42 to 93 Years), diagnosed with MM based on the International Staging System. The basis for inclusion of patients in this study was with previous untreated MM ones. The study was performed in accordance with the declaration of Helsinki. To determine whether chemotherapies for MM factors play the critical role in the development of secondary disease, simultaneously two different cultures were processed, an unstimulated 96 hours culture (U96HC) on whole BM(WBM), a short-time 24 hours culture (ST24HC) after CD138+ plasma cells (PCs) depleted on negative fraction (CD138- cells) of BM and the FISH was investigated on purified CD138+.All samples were enriched in PCs by the Automated Magnetic Cell Sorter (Miltenyi technology)proceeded with anti-CD138 specific antibodies applied. The CD138+ PCs and the CD138- cells were collected in different tubes. The CD138− cells were used for a ST24HC. FISH was performed on the purified CD138+, PCs with a recommended FISH panel (MM International Working Group). Screening was performed systematically for the following unbalanced alterations and reciprocal rearrangements: del(13)(q14)(D13S25), del(17)(p13)(TP53),+3(D3Z), +9(D9Z1), +15(D15Z14), t(4;14)(p16;q32)/IGH-FGFR3, t(11;14)(q13;q32)/IGH-CCND1 (Abbott).After observing the results of U96HC on whole BM (CD138+ and CD138− cells), ST24HC (CD138− cells) and FISH for each patient, two clone cytogenetically were distinct and unrelated chromosomal abnormalities were found in 40 (11.7%) of the 342 MM patients (6 F, 34 M; median age 74 years; range 42 to 87 Years) 34 had a MPD and 6 had a LD. A second immunophenotyping analysis confirmed the presence of those LD/MM simultaneous haematological malignancy. In the cases of the patients with MM/ MPD, the frequency of cytogenetic abnormality unrelated to the myeloma clone was respectively; the 20q deletion, detected for 13 the 34 patients, the 20q- is a sole abnormality for 12 cases and associated with a complex caryotype in 1 case. The trisomy of chromosome +8 was observed in 7 cases, the del(7q) or monosomy 7 in 5 cases, loss of gonosome Y in 4 cases, del(11) for 2 cases, translocation t(9;22) in one case, 5q abnormality in one case and trisomy 9 with JAK2 V617F mutation in one case. For the patients with MM/LD, 5 patients had a trisomy +12 and or trisomy +18 like sole abnormality or associated with others cytogenetics abnormalities and one patient had 6q deletion. Discussion, Whereas in the literature the most common cytogenetic abnormalities typifying MPD after alkylator-based therapy include partial or complete deletions of chromosomes 5, 7, and 20 as well as trisomy 8. In our study we observed those abnormalities with the same frequency for the patients had simultaneous MPD associated in untreated MM at diagnosis. Six patients had simultaneous LD and MM. The marginal zone lymphoma was confirmed for 3 patients. The CC observed a trisomy +12 for those three patients associated with +18 and +19 for 2 cases and del(13) and trisomy 3 for one among them. We demonstrated in untreated MM patients the coexistence of MM and MPD or LD at diagnosis with MPD-type or LD-type chromosome abnormalities within MM signature karyotype. We hence recommend that CC studies, 96 hours WBM, 24 hours on negative fraction CD138− cells and FISH on purified CD138+ PCs, the three should be an integral part of the evaluation of patients with MM at diagnosis into clinical trials using HDT is warranted to determine whether patients who are predisposed to developing tMDS/sAML, they can be identified prospectively. Disclosures: No relevant conflicts of interest to declare.

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Immunoglobulin D Multiple Myeloma: Disease Profile, Therapeutic Response, and Survival

Acta Haematologica ◽

10.1159/000446599 ◽

2016 ◽

Vol 136 (3) ◽

pp. 140-146 ◽

Cited By ~ 5

Author(s):

Guo-rong Wang ◽

Wan-jun Sun ◽

Wen-ming Chen ◽

Zhong-xia Huang ◽

Jia-jia Zhang ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Response Rate ◽

Cox Regression ◽

Treatment Strategies ◽

Response To Therapy ◽

Hematopoietic Stem ◽

Immunoglobulin D

Objectives: The long-term clinical characteristics, response to therapy, and survival in patients with immunoglobulin D (IgD) multiple myeloma (MM) were investigated. Methods: A retrospective study was conducted that included 68 patients treated in the last 10 years, 37 of whom received bortezomib only (bortezomib group), 13 of whom received bortezomib and underwent autologous hematopoietic stem cell transplantation (bortezomib + ASCT group), and 18 of whom received conditional chemotherapy (non-bortezomib group). Results: The ratio of males to females was 44:24, and the median age was 56.5 years. The overall response rate of each group was 91.9, 77.8, and 100%, respectively. The median overall survival (OS) and progression-free survival (PFS) were 24 and 15.5 months, respectively, among the 68 patients. The median OS of each group was 23, 21.5, and 27 months, respectively. The median PFS of each group was 18, 12, and 24 months, respectively. The 3- and 5-year OS were 64 and 45%, respectively, and the 3- and 5-year PFS were 39 and 13%, respectively, among the 68 patients. Cox regression showed that the percentage of bone marrow plasmacytosis was significantly associated with OS (p = 0.038). Conclusions: The survival of IgD patients is shorter than that of other MM patients. Treatment strategies with bortezomib followed by stem cell transplantation may boost the response rate and improve survival.

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Impact of Non High-Risk Chromosomal Abnormalities on the Outcome of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Blood ◽

10.1182/blood.v118.21.333.333 ◽

2011 ◽

Vol 118 (21) ◽

pp. 333-333 ◽

Cited By ~ 1

Author(s):

Sairah Ahmed ◽

Heather Lin ◽

Veera Baladandayuthapani ◽

Mubeen A Khan ◽

Gary Lu ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

High Risk ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Chromosomal Abnormalities ◽

High Dose Chemotherapy ◽

High Dose ◽

Hematopoietic Stem

Abstract Abstract 333 Impact of Non High-Risk Chromosomal Abnormalities on the Outcome of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Background: Despite novel therapeutic agents and high-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HCT), most patients eventually progress and die of their disease. Recent advances in cytogenetic, molecular and genomic studies have led to identification of several chromosomal and molecular abnormalities. These abnormalities are important predictors of response to therapy, progression-free survival (PFS) and overall survival (OS). On conventional cytogenetic (CC) analyses, del 13, t(4;14), t(14;16) and del 17p are considered high-risk (HR). On Fluorescence in situ hybridization (FISH) analysis, all except del 13 are considered HR (Munshi, N et al. Blood 2011 117: 4696–4700). However there are a number of chromosomal abnormalities whose significance is not clearly identified (non-HR). In this study we report the impact of these non-HR chromosomal abnormalities on the outcome of patients who received high-dose chemotherapy and auto-HCT. Methods: We performed a retrospective review of patients with multiple myeloma who underwent high dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center. Between 10/1991 and 12/2010, 1570 patients received auto-HCT. The results of CC studies were available for 1329 patients, either at diagnosis or at relapse, but before auto-HCT. The primary objective was to study the impact of non-HR chromosomal abnormalities on PFS and OS, and to compare them to patients without chromosomal abnormalities. Results: Patient characteristics and major outcomes are summarized in the attached Table. In 1329 patients with available CC analyses before auto-HCT, chromosomal abnormalities were identified in 405 (30%) patients. One-hundred and seven (7%) patients had known HR chromosomal abnormalities, while 298 (23%) patients had non-HR chromosomal abnormalities. Fifty (17%) patients with non-HR chromosomal abnormalities and 296 patients (32%) with normal CC achieved complete or stringent complete responses (CR + sCR) (p=0.0001). Median follow up in surviving patients was 36 months. Median PFS in patients with non-HR chromosomal abnormalities and normal CC were 18.2 months (95%CI: 16–22.7) and 32.7 months (95% CI: 27.8–36.3), respectively (p= <.0001) (Figure 1). The OS in patients with non-HR chromosomal abnormalities and with normal CC were 56.5 months (95% CI: 43.2–66.9) and 87.2 months (95%CI: 80.1–102.4), respectively (p= <.0001) (Figure 2). Conclusions: In this large single center study with a long follow up, we demonstrated that non-HR chromosomal abnormalities in myeloma are associated with a lower CR rate and shorter PFS and OS after auto-HCT. Further studies are needed to better define these non-HR abnormalities and their impact on prognosis. Disclosures: No relevant conflicts of interest to declare.

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A Lower Dose Of Melphalan (140 mg/m2) As Preparative Regimen For Multiple Myeloma In Patients >65 Or With Renal Dysfunction

Blood ◽

10.1182/blood.v122.21.5536.5536 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5536-5536 ◽

Cited By ~ 4

Author(s):

Ila Maewal Saunders ◽

Alison M Gulbis ◽

Richard E Champlin ◽

Muzaffar H. Qazilbash

Keyword(s):

Multiple Myeloma ◽

Renal Dysfunction ◽

Board Of Directors ◽

Response Rate ◽

Advisory Committees ◽

Hematopoietic Stem ◽

Overall Response ◽

Significant Difference ◽

Preparative Regimen ◽

Related Mortality

Abstract Background Melphalan at a dose of 200 mg/m2 IV (MEL 200) is considered the standard preparative regimen for autologous hematopoietic stem cell transplantation (auto-HCT) for multiple myeloma. However, reduced doses of melphalan such as140 mg/m2 (MEL 140) are often used in older patients or patients with renal dysfunction. Methods The purpose of this retrospective analysis was to determine if there was a difference in toxicity, treatment-related mortality (TRM), response rate, progression- free survival (PFS) or overall survival (OS) in patients that received 140 mg/m2 of melphalan (MEL 140) compared to those receiving MEL 200 for auto-HCT. From June 1, 1996 through December 31, 2012, 63 patients received MEL 140. We compared their outcomes with 252 patients that received MEL 200. Results Patient characteristics and outcomes are shown in the attached Table. Patients in the MEL 140 group were older, had a higher β2 microglobulin (β2M) level both at diagnosis and auto-HCT, and had a higher serum creatinine (Cr) at auto-HCT (Table). A higher proportion of patients in MEL 140 were older than 65 with serum Cr > 2 mg/dL. There was no significant difference in disease status or high-risk cytogenetics between the 2 groups (Table). NCI CTCv3 > III non-hematologic toxicity was not significantly different between MEL 140 and MEL 200. Transplant-related mortality (TRM) at 100 days and at 1 year was 0% and 0.4% in MEL 140 and 200 (p=1.0), respectively. Complete remission (CR) rates in MEL 140 and MEL 200 were 16% and 29%, respectively (p=0.03). There was no significant difference in (CR) + very good partial remission (VGPR), or overall response (CR + VGPR + PR) between MEL 140 and MEL 200. Median follow up in surviving patients in MEL 140 and 200 was 7.6 and 25 months, respectively. Fifteen (24%) and 64 (25%) patients died in MEL 140 and MEL 200 groups, respectively, with >90% of deaths due to recurrent disease. Median PFS was 26.4 and 30.6 months in MEL 140 and MEL 200 groups, respectively (p=0.46). Median OS was 38.4 and 93.0 months in MEL 140 and MEL 200 groups, respectively (p=0.02). However, there was no significant difference in PFS or OS in patients older than 65 or with serum Cr > 2 mg/d between MEL 140 and MEL 200. Conclusion The dose of melphalan can be safely reduced to 140 mg/m2 in patients >65 or with renal insufficiency without adversely impacting the overall response rate or PFS. Disclosures: Qazilbash: Otsuka Pharmaceuticals: Research Funding; Onyx Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millennium Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

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The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis

Blood ◽

10.1182/blood.v66.2.380.380 ◽

1985 ◽

Vol 66 (2) ◽

pp. 380-390 ◽

Cited By ~ 283

Author(s):

GW Dewald ◽

RA Kyle ◽

GA Hicks ◽

PR Greipp

Keyword(s):

Multiple Myeloma ◽

Median Survival ◽

Plasma Cell ◽

Chromosomal Abnormalities ◽

Chromosome Analysis ◽

Plasma Cell Leukemia ◽

Newly Diagnosed ◽

Cell Leukemia ◽

Chromosome 11 ◽

Cytogenetic Studies

Abstract Chromosome studies were done on 82 patients with multiple myeloma, 11 with amyloidosis, 2 with multiple myeloma and amyloidosis, and 5 with plasma cell leukemia to investigate their chromosomal abnormalities and to determine the usefulness of cytogenetic studies. A chromosomally abnormal clone was found in 29 patients but was observed most often in those with active disease: in 18% of patients with newly diagnosed multiple myeloma, in 63% with aggressive disease, and in 40% with plasma cell leukemia. Survival among the newly diagnosed patients was significantly shorter (P = .0089) for those in whom an abnormal clone was identified (median survival, six months) than for those in whom only normal metaphases were observed (median survival, greater than 12 months). Among all of the patients, survival from the time of chromosome analysis was shorter for those in whom a chromosomally abnormal clone was found: the median survival was three months for patients with all abnormal metaphases and eight months for patients with normal and abnormal metaphases and has not yet been reached for patients with only normal metaphases. The most common anomalous chromosomes in patients with a plasma cell proliferative disorder were 1, 11, and 14: 11 patients had an abnormality involving chromosome 14q32 and nine patients had an anomalous chromosome 11. The single most common abnormality, a t(11;14)(q13;q32), occurred in three patients. Among the patients who developed preleukemia or acute nonlymphocytic leukemia, the most common anomaly involved chromosome 7. The results suggest that cytogenetic studies are useful for identifying patients who have a poor prognosis and can help distinguish patients with a cytopenia because of preleukemia from those with an aggressive plasma cell proliferative process.

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The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis

Blood ◽

10.1182/blood.v66.2.380.bloodjournal662380 ◽

1985 ◽

Vol 66 (2) ◽

pp. 380-390 ◽

Cited By ~ 5

Author(s):

GW Dewald ◽

RA Kyle ◽

GA Hicks ◽

PR Greipp

Keyword(s):

Multiple Myeloma ◽

Median Survival ◽

Plasma Cell ◽

Chromosomal Abnormalities ◽

Chromosome Analysis ◽

Plasma Cell Leukemia ◽

Newly Diagnosed ◽

Cell Leukemia ◽

Chromosome 11 ◽

Cytogenetic Studies

Chromosome studies were done on 82 patients with multiple myeloma, 11 with amyloidosis, 2 with multiple myeloma and amyloidosis, and 5 with plasma cell leukemia to investigate their chromosomal abnormalities and to determine the usefulness of cytogenetic studies. A chromosomally abnormal clone was found in 29 patients but was observed most often in those with active disease: in 18% of patients with newly diagnosed multiple myeloma, in 63% with aggressive disease, and in 40% with plasma cell leukemia. Survival among the newly diagnosed patients was significantly shorter (P = .0089) for those in whom an abnormal clone was identified (median survival, six months) than for those in whom only normal metaphases were observed (median survival, greater than 12 months). Among all of the patients, survival from the time of chromosome analysis was shorter for those in whom a chromosomally abnormal clone was found: the median survival was three months for patients with all abnormal metaphases and eight months for patients with normal and abnormal metaphases and has not yet been reached for patients with only normal metaphases. The most common anomalous chromosomes in patients with a plasma cell proliferative disorder were 1, 11, and 14: 11 patients had an abnormality involving chromosome 14q32 and nine patients had an anomalous chromosome 11. The single most common abnormality, a t(11;14)(q13;q32), occurred in three patients. Among the patients who developed preleukemia or acute nonlymphocytic leukemia, the most common anomaly involved chromosome 7. The results suggest that cytogenetic studies are useful for identifying patients who have a poor prognosis and can help distinguish patients with a cytopenia because of preleukemia from those with an aggressive plasma cell proliferative process.

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Outcomes Among High Risk and Standard Risk Multiple Myeloma Patients Treated With High Dose Therapy and Autologous Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v122.21.3358.3358 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3358-3358

Author(s):

Maliha Nusrat ◽

Syed M. Kazmi ◽

Amanda Megan Cornelison ◽

Partow Kebriaei ◽

Yago Nieto ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

High Risk ◽

Chromosomal Abnormalities ◽

Poor Response ◽

Chromosome 1 ◽

High Dose ◽

Hematopoietic Stem ◽

Bone Marrow Plasma ◽

Standard Risk

Abstract Background Chromosomal analysis using conventional cytogenetics (CC) and interphase fluorescence in situ hybridization (FISH) identifies a high risk multiple myeloma population (HR-MM) characterized by poor response to chemotherapy and shorter survival. The objective of this study was to compare outcomes of autologous hematopoietic stem cell transplantation (ASCT) at our institution in HR-MM and standard risk MM (SR-MM) patients (pts) identified through CC and FISH. Methods Metaphase CC and FISH data was collected from medical records of MM pts who underwent ASCT at our institution between Jan 2005 to Dec 2009. HR-MM pts were defined if CC revealed deletion (del) of chromosome 13/13q, del17/17p, t(4;14), t(14;16), hypoploidy (<45 chromosomes excluding –Y), or chromosome 1 abnormalities [+1, -1, t(1;x)] in at least 2 metaphases; or if FISH showed del 17p, t(4;14). Kaplan & Meier method was used for assessing progression free survival (PFS) and overall survival (OS); log-rank test was used to evaluate the difference between pt groups and Cox proportional hazards models were fitted for multivariate analysis. Results Out of 670 MM pts who received ASCT during the specified time, 74 (11%) had HR-MM while 596 (89%) had SR-MM. Table 1 summarizes baseline characteristics and outcomes of HR- and SR-MM pts. In HR-MM pts, chromosome 1 aberrations were most common and seen in 53 (76%) pts while del13/13q, hypodiploidy, del17/17p and t(4;14) was found in 48 (65%), 27 (37%), 16 (22%) and 5 (9%) pts, respectively. Concurrence of high-risk chromosomal abnormalities (i.e. >1) occurred in 58% of HR-MM pts. As compared to SR-MM pts, HR-MM pts were more commonly male (72 vs. 56%), had a significantly higher bone marrow plasma cell burden at diagnosis (52 vs. 29%. p<0.001) or at time of ASCT (5 vs. 2%. p<0.000) and were refractory to treatment before undergoing ASCT (34 vs. 22%; p0.01). Melphalan 200mg/m2 was the most common conditioning regimen used and there was no difference in time to bone marrow engraftment and platelet recovery. With median follow up of 39.8 months after ASCT, HR-MM pts, as compared to SR-MM pts, had significantly lower rates of >/= PR (74 vs. 84%; p <0.01), median PFS (10.3 vs. 32.4 months p<0.001) and OS (28 vs. not reached, p<0.001). On multivariate analysis of the HR-MM pts, having only 1-high-risk cytogenetic abnormality or achieving at least very-good-partial-response (VGPR) after ASCT were factors independently associated with improved OS (p<0.002). In contrast, induction chemotherapy with bortezomib, myeloma status at time of ASCT and post-ASCT maintenance chemotherapy did not significantly affect PFS or OS. Conclusion HR-MM pts are characterized by higher bone marrow plasma cell burden, concurrence of high-risk chromosomal abnormalities, and poor response to induction or high dose chemotherapy followed by ASCT as compared to SR-MM pts. In HR-MM pts, having only 1-high risk cytogenetic abnormality or achieving at least VGPR with ASCT are independent factors associated with improved survival. Disclosures: No relevant conflicts of interest to declare.

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Melphalan-Based Autologous Transplantation in the Octogenarian Multiple Myeloma Patient Population

Blood ◽

10.1182/blood-2018-99-110241 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4608-4608 ◽

Cited By ~ 2

Author(s):

Neeraj Y Saini ◽

Romil Patel ◽

Ankur Varma ◽

Qaiser Bashir ◽

Ruby Delgado ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Maintenance Therapy ◽

Board Of Directors ◽

Research Funding ◽

Response Rate ◽

Advisory Committees ◽

Hematopoietic Stem

Abstract Abstract: Background: Upfront autologous hematopoietic stem cell transplantation (auto-HCT) combined with novel anti-myeloma drugs is considered the standard of care for transplant-eligible patients with multiple myeloma (MM). However, this treatment is generally avoided in older patients due to concerns about toxicity. MM is primarily a disease of the elderly, with >35% patients being older than 70 years of age at diagnosis. We have previously reported on the role of auto-HCT in MM patients >70 years1. In this study, we evaluate the safety and feasibility of auto-HCT in patients ≥80 years who received auto-HCT at our institution. Methods: We retrospectively reviewed the outcomes of MM patients with age ≥80 years who underwent auto-HCT between January, 2007, and June, 2018. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of auto-HCT to the last follow up or the censored date. Kaplan-Meier method was used to estimate PFS and OS. Results: Between January, 2013, and December, 2017, out of a total of 1465 MM patients referred for evaluation for auto-HCT at our institution, only 10(0.68%) were of age ≥80 years. Also, between January, 2016, and June, 2018, a total of 210 MM patients with age ≥80 years were treated at our institution, and only 3(0.14%) underwent auto-HCT. Overall among 1740 patients with MM who received an auto-HCT at our institution between the beginning of 2007 to June, 2018, 9(0.5%) patients were ≥ 80 years of age (range 80-83). Table 1 summarizes the patient characteristics of these nine patients. All patients had an ECOG performance status of either 0 or 1. The median hematopoietic stem cell transplant - comorbidity index for the cohort was 3 (range, 0-5). Eight (89%) patients were in first remission, and 1 (11%) patient had relapsed disease at auto-HCT. All patients received melphalan at a reduced dose of 140 mg/m2 as the conditioning regimen. Eight patients (89%) received maintenance therapy with lenalidomide. The median follow-up from auto-HCT was 18 months (range 0.5 - 50 months). No (0%) patient died within 100 days of auto-HCT. Out of 8 evaluable patients, 4 (50%) achieved a complete response, 2 (25%) very-good partial, and 2 (25%) achieved a partial response with an overall response rate of 100%. Eight (89%) patients were alive until the last follow-up. Median PFS was 31.5 months, while the median OS has not been reached (Fig1). 2-yr PFS and OS were 62.5% and 75% respectively. One patient died 22 months post-transplant due to non-transplant related cause. Conclusions: In selected MM patients ≥80 years old, auto-HCT was feasible, with 0% TRM, 100% response rate, and 2-year OS of 75%. Almost 90% of these patients went on to receive maintenance therapy. References: Qazilbash, M. H. et al. Autologous stem cell transplantation is safe and feasible in elderly patients with multiple myeloma. Bone Marrow Transplantation39, 279-283 (2007). Disclosures Shpall: Affirmed GmbH: Research Funding. Thomas:Celgene: Research Funding; Array Pharma: Research Funding; Acerta Pharma: Research Funding; Amgen Inc: Research Funding; Bristol Myers Squibb Inc.: Research Funding. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Patel:Poseida Therapeutics, Inc.: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Celgene: Research Funding. Orlowski:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium Pharmaceuticals: Consultancy, Research Funding; BioTheryX, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Poseida: Research Funding; Bristol Myers Squibb: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy. Champlin:Otsuka: Research Funding; Sanofi: Research Funding.

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