A Comparative Study Of The Outcome Of Isolated Chromosome 13q and Clonal Progression Detected By I-FISH Do Additional Cytogenetic Abnormalities Impact Survival In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2160-2160
Author(s):  
Edward Peres ◽  
Shatha Farhan ◽  
Philip Kuriakose ◽  
Susan Michalowski ◽  
Alexandra Sitarik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Cytogenetic Abnormalities ◽  
Chromosome 13Q

Abstract Background Chromosomal abnormalities detected by interphase fluorescence in situ hybridization (I-FISH) are an important prognostic marker in patients with multiple myeloma (MM). Isolated chromosome 13q has been considered standard risk when identified by I-FISH and high risk by conventional cytogenetics. The impact of additional cytogenetic abnormalities with chromosome 13q identified by I-FISH in regards to prognosis has not been fully defined. In this report, we describe the outcome of patient’s with multiple myeloma with isolated chromosome 13q and 13q+ (additional cytogenetic abnormalities) identified by I-FISH at our institution between January 2003 and January 2013 and had I-FISH analysis prior to treatment. Methods The primary objective was to compare patient’s outcomes in regards to response, time to progression, and overall survival between patients who had an isolated 13q and 13q+ identified by I-FISH in the bone marrow plasma cells. Kaplan & Meier curves were generated to calculate overall survival (OS) between the two groups. Results Between January 2003 and January 2013, we identified 76 patients by I-FISH who had either an isolated 13q or 13q+ in patients with multiple myeloma (Patient characteristics Table 1). Of the patients with an isolated 13q abnormality 33% received a bortezomib-based regimen and 38% in the 13q+ group. Of the patient’s with a isolated 13q 38% went onto receive high dose chemotherapy followed by autologous stem cell transplant (ASCT) while 20% with a 13q+ received ASCT. African American patients with 13q consisted of 65% and 60% with 13q+ in our patient population. For the 13q or 13q+ who underwent high dose chemotherapy followed by autologous stem cell transplant OS was 85% compared to the non-transplant group 45% (p=0.01) (Figure 2). On follow up at a median of 2.5 years mortality occurred in 31% of the 13q patients compared to 62% in the 13q+ group. The overall survival at 5 years was 25% in the 13q+ group compared to 65% in the patient’s with an isolated 13q, With the 13q+ group having an overall poor OS (p=0.03) Conclusion Patients who harbor the 13q and additional cytogenetic abnormalities identified by I-FISH have a significant worse outcome compared to patients with an isolated 13q. These patients should be considered high risk and consideration for treatment with novel agents and autologous stem cell transplant followed by post-transplant maintenance therapy should be considered. Disclosures: No relevant conflicts of interest to declare.

Role of High-Dose Chemotherapy with Autologous Stem Cell Transplantation in Primary Systemic Amyloidosis: A Systematic Review and Meta-Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2872-2872
Author(s):  
Madhusmita Behera ◽  
Ambuj Kumar ◽  
Mohamed A. Kharfan-Dabaja ◽  
Benjamin Djulbegovic
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Meta Analysis ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Conventional Chemotherapy

Abstract Background: Primary systemic amyloidosis (AL) is a rare plasma cell clonal disorder(8/million) characterized by extracellular deposits of material composed mainly of fragments of light chain immunoglobulin throughout a body. Standard chemotherapy (e.g. melphalan and prednisone) is associated with poor outcomes (typical median survival is between 12–18 months with less than 5% survive 10 years). Autologous stem cell transplant (ASCT) has been increasingly advocated for treatment of AL. However, it is uncertain whether ASCT is better than standard chemotherapy. To address this uncertainty, we undertook a systematic review/meta-analysis to evaluate the efficacy of high-dose chemotherapy and autologous stem-cell transplant (HSCT) versus conventional chemotherapy in patients with AL. Methods: Data search of published studies included Medline [all randomized controlled trials (RCTs)], Cochrane library and hand search of references. Studies were included if they were comparison trials of HSCT versus conventional chemotherapy, regardless if they were RCTs, prospective studies with historical control, or single arm studies. The studies were eligible if patients had biopsy proven AL with at least one major organ involved. Data were extracted on benefits as well as harms (overall survival, event-free survival, response, treatment related mortality, treatment-related morbidity). Results: Out of 34 identified studies only 13 met the inclusion criteria for the current systematic review (2 RCTs, 2 prospective non-randomized trials involving historical control, and 9 single arm trials). Altogether these trials enrolled 1056 patients. Pooled data from 4 trials with controls (RCT and non-RCT) found similar overall survival for ASCT and conventional therapy arms [hazard ratio (HR) of 1.10 (95% CI 0.88, 1.36, p=0.4); p= 0.6]. Analysis of data according to trial design also did not find any difference in survival [HR for RCTs was 1.10 (95% CI 0.88, 1.37) and for non RCTs HR was 0.98 (95% CI 0.29, 3.35)]. The complete hematological response was also similar in both arms in RCTs (Odds ratio [OR]=1.38, 95%CI 0.67, 2.85; p=0.4) and non RCTs (OR=1.78, 95%CI 0.22, 14.65; p=0.32). The pooled proportion of treatment-related deaths in the single arm studies for AHCT was 0.119 (95% CI = 0.09 to 0.14)]. Conclusion: The results from the meta-analysis indicate that there is no statistically significant difference between the treatment effects from high-dose chemotherapy with ASCT and conventional chemotherapy. Hence, the efficacy of ASCT in improving overall survival and complete hematological response remains to be proven.

Incidence of Adrenal Insufficiency in Patients with Multiple Myeloma during High Dose Chemotherapy and Autologous Stem Cell Transplant

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5862-5862 ◽  
Author(s):  
Ahmad Hatem Mattour ◽  
Shatha Farhan ◽  
Nalini Janakiraman ◽  
Edward Peres
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Adrenal Insufficiency ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
Adrenal Function ◽  
High Dose ◽  
Cell Transplant ◽  
Cortisol Levels

Abstract Background High dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) is considered the standard of care for patients with multiple myeloma (MM). With most patients receiving induction therapy that includes corticosteroids. The combined effect of prior therapy for myeloma and ASCT related complications may result in hypotension and require intensive medical treatment. To date the incidence of adrenal insufficiency in the setting of ASCT is unknown. The effects of this underlying disorder in regards to post transplant outcome remain unknown as well. We set out to compare the outcomes of patients with multiple myeloma who underwent ASCT with adrenal insufficiency compared to those with sufficient adrenal function. Methods We undertook a prospective study in 13 consecutive patients with Multiple Myeloma admitted for high dose chemotherapy and autologous stem cell transplant at Henry Ford Hospital between February 2014 through June 2014, with the first patient sample being obtained in on 2/14/2014 and last sample recorded in 6/23/2014. Random cortisol levels were obtained on the day of admission or day -2 (figure 1), prior to the start of high dose chemotherapy. All prior therapies included corticosteroids and consisted of the following RVD, DCEP, RD, VD, DT-PACE. Patients were classified into two groups those with cortisol levels > 5 and those patients who had cortisol levels <5. Endpoints analyzed included hypotension, septic shock, and duration of antibiotic therapy. Results Of the 13 patients analyzed the median age was 60 years old (range 53-78), gender 8 male patients 5 female. All patients underwent high dose chemotherapy with Melphalan and Autologous stem cell transplant. Of the 13 patients in which data was obtained 3/13 23% had adrenal insufficiency prior to high dose Melphalan and ASCT. With a median cortisol level of 3.2 in the patient cohort who were found to be adrenal insufficient. The incidence of hypotension was 2/3 66% in the adrenal insufficient patients compared 1/10 10% in the cohort with sufficient adrenal function. Septic shock occurred in 2/3 66% of the adrenal insufficient compared to 0/10 in the adrenal sufficient group. The median duration of antibiotic therapy was 5 days in the adrenal insufficient cohort compared to 2 days in the patients with adequate adrenal function. Conclusion In this small cohort of consecutive patients from a single center, we found that there was a high incidence of adrenal insufficiency 23% in patients undergoing ASCT. The treatment regimens varied in the study group with all patients receiving corticosteroid therapy in there induction regimen. Given the unexpectedly high incidence of adrenal insufficiency a consideration should be given to check a random cortisol level prior to the initiation of HDC. Supplemental therapy or treatment should be considered in this high risk group to avoid unnecessary complications and prolonged antibiotic use and supportive care in this patient cohort. Figure 1. Random Cortisol levels obtained prior to Autologous stem cell transplant Figure 1. Random Cortisol levels obtained prior to Autologous stem cell transplant Disclosures No relevant conflicts of interest to declare.

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