Effect Of Comorbidities In Myelodysplastic Syndrome By Revised-IPSS and Age

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1530-1530
Author(s):  
Naval G. Daver ◽  
Kiran Naqvi ◽  
Tapan M. Kadia ◽  
Courtney D. DiNardo ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Myelodysplastic Syndrome ◽  
Median Survival ◽  
Research Funding ◽  
Comorbidity Score ◽  
Kaplan Meier ◽  
Comorbidity Scores ◽  
Severe Comorbidity ◽  
Very High

Abstract Background Comorbidites play a crucial role in the prognosis, treatment and outcomes of patients with hematological malignancies. We have previously reported the impact of comorbidities independent of age and IPSS score (1). The aim of this study was to determine whether comorbidities continued to have a similar impact when patients were reclassified according to the Revised-International Prognostic Scoring System (RIPSS). Methods We reviewed the medical records of 600 consecutive MDS patients who presented to MD Anderson Cancer Center from January 2002 to June 2004. The Adult Comorbidity Evaluation-27 (ACE-27), a validated 27-item comorbidity index for cancer patients (2), was used to assess the severity of comorbid conditions. For each patient, we obtained demographic data and specific staging information based on the R-IPSS. We also collected information on stem cell transplantation (SCT), mortality and survival. Kaplan-Meier methods and log-rank tests were used to assess survival. Results Of the 600 patients included in this study, 402 (67%) were male, and 517 (86%) were white; median age at presentation was 66 years (17 – 94); mean duration of follow-up was 54 months (1 - 100). A total of 34, 117, 131, 129, 165 patients were R-IPSS very low, low, intermediate, high and very high respectively. The ACE-27 comorbidity scores were as follows: none, 137 patients (23%); mild, 254 (42%); moderate, 127 (21%); and severe, 82 (14%). 476 (79%) patients died, and 54 (9%) patients underwent SCT. Overall median survival using the Kaplan-Meier method was 16 months (1 – 100). Median survival according to ACE-27 scores was: 28 months for no comorbidity, 16 months for mild comorbidity, 14 months for moderate comorbidity, and 9 months for severe comorbidity with a P-value of P<0.001. The median survival by R-IPSS was 47 , 34, 21, 16, 6 months for patients in very low, low, intermediate, high and very high risk groups respectively (P<0.001). Of the 54 patients who had SCT, 27 (50 %) died. The median survival of patients who did not undergo stem cell transplantation was 23, 16, 4, 8 months for patients with no, mild, moderate and severe comorbidity scores, respectively (P<0.001). The ACE-27 comorbidity score significantly impacted the median OS of patients in the intermediate (P<0.001) , high (P=0.045) , and very high (P=0.004) R-IPSS groups; but did not significantly impact the median OS in the low (P=0.11) and very low (P=0.49) groups. See figures 1 – 5 below. The ACE-27 comorbidity score significantly impacted the median OS of patients </=65 years (P<0.001) but did not significantly impact those >65 years (P=0.18). Conclusion Comorbidities had a significant impact on the survival of patients with myelodysplastic syndrome, especially among those with more advanced disease and younger age (</= 65). Among the intermediate, high and very high R-IPSS groups the patients with higher ACE-27 comorbidity scores had a significantly shorter survival than those with no comorbidities. The comorbidity scores did not significantly impact survival in the R-IPSS very low and low groups, which may reflect the improved survival and limited number of events that occur in these favorable subsets. Perhaps with longer follow-up a difference in survival may emerge among the favorable R-IPSS subsets. A comprehensive assessment of comorbidity is therefore needed to determine the prognosis in patients with MDS. References 1. Naqvi K, Garcia-Manero G, Sardesai S. Association of comorbidities with overall survival in myelodysplastic syndrome: Development of a prognostic mode. J Clin Oncol. 2011;29(16):2240-6. 2. Piccirillo JF, Tierney RM, Costas I, et al. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA. 2004;291:2441-47. Disclosures: Ravandi: Sunesis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Teva: Consultancy, Honoraria; Pfizer: Honoraria; Merck: Research Funding; Bayer/Onyx: Consultancy, Honoraria; EMD Serono: Research Funding; Medimmune: Research Funding; Amgen: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Garcia-Manero:Novartis Pharmaceutical: Research Funding. Kantarjian:Sanofi-Aventis: Research Funding.

Comorbidities and Myelodysplatic Syndromes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2789-2789 ◽  
Author(s):  
Kiran Naqvi ◽  
Guillermo Garcia-Manero ◽  
Sagar Sardesai ◽  
Jeong Oh ◽  
Sherry Pierce ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Median Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Comorbidity Scores ◽  
Severe Comorbidity

Abstract Abstract 2789 Poster Board II-765 Background: Cancer patients often experience comorbidities that may affect their therapeutic options, prognosis, and outcome (1). Limited studies have evaluated the characteristics and impact of comorbidities in myelodysplastic syndromes (MDS). The aim of this study was to determine the effect of comorbidities on the survival of patients with MDS. Methods: We reviewed the medical records of 500 consecutive MDS patients who presented to MD Anderson Cancer Center from January 2002 to June 2004. The Adult Comorbidity Evaluation-27 (ACE-27), a validated 27-item comorbidity index for cancer patients (2), was used to assess the severity of comorbid conditions. For each patient, we obtained demographic data and specific staging information based on the International Prognostic Scoring System (IPSS). We also collected information on stem cell transplantation (SCT), mortality and survival. Kaplan-Meier methods and log-rank tests were used to assess survival. Multivariate analysis was performed using the Cox Proportional Hazards Model. Results: Of the 500 patients included in this study, 327 (65.4%) were male, and 436 (87.9%) were white; median age at presentation was 66.6 years (17.7, 93.5); mean duration of follow-up was 23.5 months (0, 88). A total of 49% of patients had IPSS intermediate-1 or lower risk. The ACE-27 comorbidity scores were as follows: none, 106 patients (21.2%); mild, 213 (42.6%); moderate, 108 (21.6%); and severe, 73 (14.6%). Three hundred and eighty one (76.2%) patients died, and 44 (8.8%) patients underwent SCT. Overall median survival using the Kaplan-Meier method was 17.6 months. Median survival according to ACE-27 scores was: 27.9 months for no comorbidity, 18.9 months for mild comorbidity, 15.2 months for moderate comorbidity, and 9.7 months for severe comorbidity. This trend reached statistical significance (p < 0.0001). The median survival by IPSS ranged from 40.9 months for patients in the low risk group versus 8.1 months for those in the high risk category (p < 0.0001). The hazards ratio obtained from the multivariate Cox Proportional Hazards Model was 1.5 and 2.0 for moderate and severe comorbidity scores when adjusted for age and IPSS (p < 0.0001). A linear trend was also observed between the severity of comorbidity and having received SCT (p = 0.001). Of the 44 patients who had SCT, 21 (47.7%) died. The median survival of patients who did not undergo stem cell transplantation ranged from 22.7 months for patients with no comorbidity to 9.3 months for patients with severe comorbidity (p = 0.0002). Conclusion: Comorbidities had a significant impact on the survival of patients with myelodysplastic syndrome. Patients with higher ACE-27 comorbidity scores had a shorter survival than those with no comorbidity, independent of their age and the IPSS risk group. Also patients with comorbid conditions received SCT less often than those without comorbidity. A comprehensive assessment of comorbidity is therefore needed to determine the prognosis in patients with MDS. References: (1) Extermann M. Measurement and impact of comorbidity in older cancer patients. Crit Rev Oncol Hematol. 2000;35:181-200. (1) Piccirillo JF, Tierney RM, Costas I, et al. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA. 2004;291:2441-47. Disclosures: No relevant conflicts of interest to declare.

Survival, Prognostic Factors, and Rates of Leukemic Transformation in a Multicenter Study of 303 Untreated Patients with MDS and Del(5q).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 945-945 ◽  
Author(s):  
Ulrich Germing ◽  
Michael Lauseker ◽  
Barbara Hildebrandt ◽  
Argiris Symeonidis ◽  
Jaroslav Cermak ◽  
...  
Keyword(s):  
High Risk ◽  
Median Survival ◽  
Research Funding ◽  
Risk Group ◽  
Competing Risk ◽  
Refractory Anemia ◽  
Red Cell ◽  
Kaplan Meier ◽  
Red Cell Transfusion

Abstract Abstract 945 In 2001, the WHO defined the category MDS with del(5q) due to unique cytogenetic, morphologic, hematologic, clinical, prognostic and therapeutic features. The survival of these patients, as well as patients with refractory cytopenia with unilineage dysplasia (RCUD) and refractory anemia with ring sideroblasts is favorable in comparison to other MDS types. Data on disease progression to a more advanced MDS category or to acute leukemia (AML) are sparse and have not been examined in detail. In order to address this issue we collated data of all patients with MDS and del(5q) characterized by low or intermediate-1 IPSS risk score that had been included into various collaborating MDS registries. Patients were followed from diagnosis and data on cell counts, transfusion dependency, and MDS progression were documented. No patients received treatment other than best supportive care. The status of 62 patients was censored at the time of the initiation of Lenalidomide therapy. AML progression was defined as >20% marrow blasts. Estimates of survival probability were calculated with the Kaplan-Meier method. The cumulative incidence of progression to AML was calculated both with the Kaplan-Meier method and with the competing risk method where “death without progression to AML” is considered as competing event, not as censoring. For both events the cumulative incidences are estimated simultaneously. This method has the advantage that it takes into account that there is a difference between end of follow-up and death. Depending on the number of competing events, the curves are lower than those calculated with the Kaplan-Meier estimator. We identified 303 patients, median age at diagnosis 65 years (28-91), 71% were females. Median follow up time was 3 years. Median survival was 71.5 months. Patients with del(5q) as a sole chromosomal aberration had a median survival of 73 months as compared to 19.3 months in patients with more than 1 additional aberrations. Patients who had red cell transfusion need at diagnosis had a median survival of 39 months vs. 97 months in transfusion independent patients (p=0.00005). Transfusion need at diagnosis was the most important parameter for survival. Patients in the WPSS very low risk group had a median survival of 107 months, as compared to 73 and 56 months in the low and intermediate risk group and 37 months in the high risk group. 44 of the 303 patients (15%) progressed to AML (>20% marrow blasts). The cumulative AML progression rate calculated with the Kaplan-Meier method was 7% at 2 years and 18.2% at 5 years. The cumulative risk of AML progression calculated with the competing risk method was 6.6% at 2 years and 15.1% at 5 years. Factors associated with the risk of AML transformation were intermediate-I IPSS risk and high risk WPSS score, marrow blast count >5%, and red-cell transfusion need at diagnosis. Survival and progression rates did not differ among the participating centers. In conclusion, survival of patients with MDS and del(5q) is high and is comparable to patients with RCUD and RARS, but is associated with a risk of AML-transformation similar to RCMD without del(5q). Further cytogenetic and molecular studies are warranted in order to identify patients at greater risk of progression. Disclosures: Germing: Novartis, Celgene: Honoraria, Research Funding. Lauseker:Celgene: Research Funding. Hildebrandt:Celgene: Research Funding. Symeonidis:Celgene: Research Funding. Cermak:Celgene: Research Funding. Pfeilstöcker:Celgene: Research Funding. Nösslinger:Celgene: Research Funding. Sekeres:Celgene: Research Funding. Maciejewski:Celgene: Research Funding. Haase:Celgene: Research Funding. Schanz:Celgene: Research Funding. Seymour:Celgene: Research Funding. Weide:Celgene: Research Funding. Lübbert:Celgene: Research Funding. Platzbecker:Celgene: Research Funding. Valent:Celgene: Research Funding. Götze:Celgene: Research Funding. Stauder:Celgene: Research Funding. Blum:Celgene: Research Funding. Kreuzer:Celgene: Research Funding. Schlenk:Celgene: Research Funding. Aul:Celgene: Research Funding. Kündgen:Celgene: Research Funding. Hasford:Celgene: Research Funding. Giagounidis:Celgene: Research Funding.

Association of Increased Ring Ssideroblasts with Inferior Survival in Patients with Myelodysplastic Syndrome with Multi-Lineage Dysplasia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5530-5530
Author(s):  
Hiroshi Kawabata ◽  
Kaoru Tohyama ◽  
Akira Matsuda ◽  
Kayano Araseki ◽  
Tomoko Hata ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Myelodysplastic Syndrome ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Who Classification ◽  
Pharmaceutical Research ◽  
Ethics Committee ◽  
Hematopoietic Stem

Abstract Myelodysplastic syndrome (MDS) is a heterogeneous group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis and a high propensity to transform into acute myeloid leukemia (AML). Although hematopoietic stem cell transplantation can cure some MDS patients, most patients are not eligible to undergo the treatment because of advanced age or comorbidities. In order to choose the optimal treatments, predicting prognosis is crucial. Chromosomal karyotype, bone marrow (BM) blast percentage, and cytopenia are well-known prognostic factors for MDS patients. These factors are incorporated into the international prognostic scoring system and its revised version (IPSS-R). However, the impact of morphological abnormalities has not been fully determined. Thus, to elucidate this, we examined the influence of the number of dysplastic lineages and the presence of increased ring sideroblasts (RS) on the survival of MDS patients whose BM blast percentages were <5%. Since 2006, the National Research Group on Idiopathic Bone Marrow Failure Syndromes, Japan, has been conducting the Prospective Registration, Central Review and Follow-up Study for Aplastic Anemia and Myelodysplastic Syndrome. Patients with BM blasts of <5% were subjected to our central review system for final diagnosis, and their medical records were collected every 6 months after their registration. By using this depository database, we retrospectively analyzed overall survival (OS) and cumulative incidence of progression to AML. This study was performed in accordance with the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Kyoto University Graduate School and Faculty of Medicine and by the ethics committee of each participating institution. Either t test or Mann-Whitney U test was used as appropriate for analyzing the differences in variables between the groups. The Kaplan-Meier method and log-rank test were used for analyzing differences in OS between the groups. The Cox proportional hazards model was used for analyzing risk factors for OS, and Grayfs test was used for analyzing differences in cumulative incidence of progression to AML. P values of <0.05 was considered statistically significant. By May 2016, 351 cases had been registered to the depository. After central review, 216 cases were diagnosed as MDS according to definition by the French-American-British Cooperative Group. Cases that were not registered within 1 year after the time of institutional diagnosis and cases with follow-up periods of <4 weeks were excluded from this study. In the 2008 WHO classification, 30 cases were RCUD (MDS-SLD in the 2016 WHO classification) and 78 were RCMD (MDS-MLD in the 2016 WHO classification). The median ages of patients with RCUD and RCMD were 67.5 and 71.5 years, respectively (P = 0.11). The male-to-female ratios were 1.14 and 2.25, respectively (P = 0.18), and the median follow-up times of the survivors were 45 and 24 months, respectively (Table 1). Among patients with RCMD, 22 showed >15% RS in erythroblasts. The mean BM blast percentage was significantly lower in patients with RCUD than in those with RCMD, consistent with the result of our pervious study that used a different cohort where the BM blast percentages in patients with RA according to the 2008 WHO classification were significantly lower than those in patients with RCMD (Matsuda A, et al. Eur J Haematol. 2013;90:79-80). The 2-year OS of patients with RCUD was significantly higher than that of patients with RCMD (84% vs 76%, P = 0.014; Fig. 1a), which is consistent with the results of a German study (Maassen A, et al. Leuk Res. 2013;37:64-70). The cumulative incidence of progression to AML tended to be higher in RCMD than in RCUD, although the difference was not statistically significant (P = 0.0656, Fig. 1b). Among patients with RCMD, those with increased number of RSs showed significantly lower hemoglobin levels and higher cytogenetic scores according to the IPSS-R definition than those without increased RS (Table 2). The 2-year OS of the former was significantly inferior to that of the latter in our cohort (58% vs 87%, P = 0.009; Fig. 1c). Increased number of RSs is known to be associated with SF3B1 mutations, which in turn have been shown to be associated with favorable prognosis. However, the results of the present study indicate that in RCMD, an increase in the number of RSs may be an unfavorable indicator of patient survival. Disclosures Ozawa: Celgene Japan: Consultancy; Sumitomo Dainippon Pharma Co. Ltd: Research Funding; JCR Pharmaceutical Inc: Consultancy; Takara Bio Inc: Research Funding. Takaori-Kondo:Pfizer: Research Funding; Eisai: Research Funding; Takeda Pharmaceutical: Research Funding; Astellas Pharma: Research Funding; Kyowa Kirin: Research Funding; Cognano: Research Funding; Toyama Chemical: Research Funding; Mochida Pharmaceutical: Research Funding; Shionogi: Research Funding; Alexion Pharmaceuticals: Research Funding; Chugai Pharmaceutical: Research Funding; Janssen Pharmaceuticals: Speakers Bureau; Merck Sharp and Dohme: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau.

scholarly journals Association of Comorbidities With Overall Survival in Myelodysplastic Syndrome: Development of a Prognostic Model

2011 ◽  
Vol 29 (16) ◽  
pp. 2240-2246 ◽  
Author(s):  
Kiran Naqvi ◽  
Guillermo Garcia-Manero ◽  
Sagar Sardesai ◽  
Jeong Oh ◽  
Carlos E. Vigil ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Median Survival ◽  
Prognostic Model ◽  
Cox Regression ◽  
Risk Groups ◽  
International Prognostic Scoring System ◽  
Cancer Center ◽  
Kaplan Meier ◽  
Severe Comorbidity ◽  
Md Anderson

Purpose Patients with cancer often experience comorbidities that may affect their prognosis and outcome. The objective of this study was to determine the effect of comorbidities on the survival of patients with myelodysplastic syndrome (MDS). Patients and Methods We conducted a retrospective cohort study of 600 consecutive patients with MDS who presented to MD Anderson Cancer Center from January 2002 to December 2004. The Adult Comorbidity Evaluation-27 (ACE-27) scale was used to assess comorbidities. Data on demographics, International Prognostic Scoring System (IPSS), treatment, and outcome (leukemic transformation and survival) were collected. Kaplan-Meier methods and Cox regression were used to assess survival. A prognostic model incorporating baseline comorbidities with age and IPSS was developed to predict survival. Results Overall median survival was 18.6 months. According to the ACE-27 categories, median survival was 31.8, 16.8, 15.2, and 9.7 months for those with none, mild, moderate, and severe comorbidities, respectively (P < .001). Adjusted hazard ratios were 1.3, 1.6, and 2.3 for mild, moderate, and severe comorbidities, respectively, compared with no comorbidities (P < .001). A final pognostic model including age, IPSS, and comorbidity score predicted median survival of 43.0, 23.0, and 9.0 months for lower-, intermediate-, and high-risk groups, respectively (P < .001). Conclusion Comorbidities have a significant impact on the survival of patients with MDS. Patients with severe comorbidity had a 50% decrease in survival, independent of age and IPSS risk group. A comprehensive assessment of the severity of comorbidities helps predict survival in patients with MDS.

Inotuzumab Ozogamicin in Combination with Low-Intensity Chemotherapy (mini-hyper-CVD) As Salvage Therapy for Adult Patients with Refractory/Relapse (R/R) Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 964-964
Author(s):  
Elias Jabbour ◽  
Susan O'Brien ◽  
Deborah A. Thomas ◽  
Koji Sasaki ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Survival ◽  
Research Funding ◽  
Response Rate ◽  
Early Death ◽  
Post Transplantation ◽  
Inotuzumab Ozogamicin ◽  
Improve Outcome ◽  
Low Intensity

Abstract Background: Outcome of pts with R/R ALL is poor. Addition of IO to effective low-intensity chemotherapy might improve outcome. CD22 expression occurs in >90% of pts with ALL. Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody bound to a toxin, calecheamicin, and has shown single-agent activity in relapsed/refractory ALL with a response rate of 58% and median survival of 6.3 months. The addition of targeted non-myelosuppressive therapy to effective low-intensity chemotherapy might further improve outcome. Methods: Pts ≥18 years with R/R ALL were eligible. The chemotherapy was lower intensity than conventional hyper-CVAD and referred to as mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x 4 doses). Rituximab and intrathecal chemotherapy were given for first 4 courses. IO was given on Day 3 of each of the first 4 courses. Pts received IO at 1.8 mg/m2 for cycle 1 followed by 1.3 mg/m2 for subsequent cycles. Results: Thirty-five pts (14 men, 21 women) have been treated so far. Pts characteristics and outcome are summarized in Table 1. Median age is 35 yrs (range 9-87). Median follow-up is 10 months (mos). The overall response rate was 71%: 18 (51%) CR, 6 (17%) CRp, and 1 (3%) marrow CR. Four (11%) pts were refractory and early death was reported in 6 (17%) pts. Grade 3-4 non-hematological toxicities included infections, mucositis, increased LFTs, and VOD (1 on study who had prior allogeneic stem cell transplantation, 3 were post transplantation following IO therapy). Four (11%) pts were switched early to maintenance therapy due to poor functional status (n=1), infectious complications (n=2), and prolonged myelosuppression (n=1). Twelve (34%) pts proceeded to receive allogeneic stem cell transplantation; of the rest, 6 (17%) relapsed within 3 mos (range, 1 to 7). At the last follow-up, 17 pts (49%) are alive, 18 (51%) died: 6 early death (3 hemorrhage, 2 sepsis, and 1 unknown cause); 8 were responders (5 died post relapse after subsequent salvage, 2 died post transplantation VOD in 1, and 1 died due to sepsis and multiple organ failure), 4 were refractory and died of disease progression. The 6-month PFS and OS rates were 79% and 58%, respectively. Median survival for pts with CR/CRp/marrow CR was 14 mos versus less than 1 mo in pts with refractory disease. Furthermore, median survival was not reached in pts with S1, 4 mos in pts with S2 and 5 mos in pts with S3+. Conclusions: The combination of IO with low-intensity mini-hyper-CVD chemotherapy is effective and shows encouraging results (71% ORR) in pts with R/R ALL. Pts with previous liver damage and transplant candidate should be considered carefully for this treatment to minimize the risk of VOD.Table 1Patient characteristics and outcomeParameterCategoryN (%)/Median [Range]Follow-up (mos)10 [1-14]Age (yrs)35 [9-87]Performance Status (ECOG)0-130 (86)Salvage StatusS119 (54)S1, primary refractory4 (12)S1, CRD1 <12 mos8 (23)S1, CRD1 ≥12 mos7 (20)S28 (23)≥ S38 (23)KaryotypeDiploid8 (23)T(4;11)5 (14)Miscellaneous16 (46)Insufficient metaphases6 (17)CD2296 [29-100]CD20≥ 20%5 (14)CR18 (35)CRp6 (17)Marrow CR1 (3)No response4 (11)ORR25 (71)Early death6 (17)6-months PFS %79Median (months)Not reached6-month OS %58Median (months)7 Disclosures Kadia: GSK: Research Funding; ARIA: Honoraria. Kantarjian:ARIAD: Research Funding; Pfizer: Research Funding; Amgen: Research Funding.

scholarly journals Outcome of Autologous Stem Cell Transplantation in Waldenström's Macroglobulinemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2149-2149
Author(s):  
Romil Patel ◽  
Neeraj Y Saini ◽  
Ankur Varma ◽  
Omar Hasan ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees ◽  
First Remission ◽  
Relapsed Disease

Abstract Introduction: The role of autologous hematopoietic stem cell transplantation (auto-HCT) in the management of patients with Waldenström Macroglobulinemia (WM), a rare, indolent lymphoma, has not been established. We had previously published our experience with auto-HCT in a small cohort of WM patients1. Here, we present an updated analysis of auto-HCT with a larger cohort of WM patients. Methods and study population: The study cohort was comprised of 29 patients who underwent high-dose chemotherapy and auto-HCT at MD Anderson Cancer Center (MDACC). The Kaplan-Meier method was used to create survival curves. Overall survival (OS) was defined as the duration from date of transplant to death or last date of follow-up in living patients. Progression-free survival (PFS) was defined as the duration from date of transplant to either progressive disease or death, whichever occurred first. Results: Median age at auto-HCT was 60 (range, 43-75 years). Eight patients (28%) had concurrent light chain amyloidosis (AL). Of the five patients who had MYD88 testing completed, 3 were positive for the MYD88 mutation. Additionally, of these 3 patients, 2 were also positive for CXCR4 mutation. Patients received a median of 2 lines (range 1-6) of therapy prior to auto-HCT; 3(10%) patients had primary refractory disease, 8(28%) were in first remission, and 18 (62%) had relapsed disease. Median time from transplant to last follow-up for the surviving patients was 5.3 years. Preparative regimens received by the patients were: Melphalan (n=20), BEAM-R (n=2), Busulfan/Melphalan (n=1), Cyclophosphomaide/Etoposide/total body irradiation (n=1), Thiotepa/Busulfan/Cyclophosphamide (n=1), and Carmustine/Thiotepa (n=1). Three patients further went on to receive allogeneic transplant either after relapse from auto-HCT or due to disease transformation to aggressive lymphoma. Twenty-eight patients achieved engraftment with a median time to neutrophil engraftment of 11 days (range, 10-15 days). One patient suffered primary graft failure due to progression of disease and died 84 days after transplant. Non-relapse mortality was 3.4% at 1 year. All patients were eligible for response evaluation. The median OS from diagnosis was 12.2 years. Overall response rate was 96%: complete response (n=8, 27.6%), very good partial response (n=5, 17.3%), partial response (n=15, 51.7%), and progressive disease (n=1, 3.4%). PFS and OS at 5 years were 43.3% and 62.9%, respectively. Median PFS and OS from auto-HCT were 4.1 and 7.3 years (Fig. 1A). The median OS from auto-HCT in first remission + primary refractory and relapsed disease was 8.2 years and 4.1 years, respectively.16 patients were alive at the time of censoring while 13 patients had died. Causes of death include relapsed disease (n=6), secondary malignancy (n=2), infection (n=1), chronic graft-versus-host disease (n=1), and unknown (n=3). 8 patients (28%) were positive for concurrent AL amyloidosis. The sites of amyloid involvement were kidneys (n=2), lungs (n=1), bone marrow (n=1), heart(n=1), lymph nodes(n=1), gastrointestinal tract (n=1) and subcutaneous fat aspirate(n=5). The median overall survival for patients with amyloid involvement (n=8) was 12 years. On univariate analyses, the number of chemotherapy regimens prior to transplant (≤ 2 vs >2 lines) was the strongest predictor of overall survival (p=0.03, HR 0.3, CI: 0.09-0.9, log-rank) and PFS (p=0.001, HR 0.24, CI: 0.07-0.85, log-rank). The median PFS in patients with ≤ 2 lines and > 2 lines of therapy was 71 months versus 19 months, respectively (Fig. 1B). Conclusion: Auto-HCT is safe and feasible in selected patients with WM, with a high response rate and durable remission even in patients with relapsed or refractory disease. References: Krina Patel et.al. Autologous Stem Cell Transplantation in Waldenstrom's Macroglobulinemia. Blood 2012 120:4533; Disclosures Thomas: Celgene: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Array Pharma: Research Funding; Amgen 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. Orlowski:Takeda: Consultancy; Celgene: Consultancy; Spectrum Pharma: Research Funding; Janssen: Consultancy; Kite Pharma: Consultancy; Sanofi-Aventis: Consultancy; BioTheryX: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. Patel:Poseida Therapeutics, Inc.: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Celgene: Research Funding.

scholarly journals Patterns of Care and Outcomes Among Older Patients with Myelofibrosis: A Population-Based Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Shelby Meckstroth ◽  
Rong Wang ◽  
Xiaomei Ma ◽  
Nikolai A. Podoltsev
Keyword(s):  
Median Survival ◽  
Research Funding ◽  
Multivariable Analysis ◽  
Population Based ◽  
Janus Kinase ◽  
Patterns Of Care ◽  
Age At Diagnosis ◽  
Jak Inhibitor ◽  
Risk Of Death

Background: Myelofibrosis (MF) is a Philadelphia chromosome negative myeloproliferative neoplasm associated with systemic and splenomegaly-related symptoms, cytopenias and decreased survival. Approval of ruxolitinib, an oral janus kinase (JAK)-inhibitor, for higher-risk MF patients (pts) by the Food and Drug Administration in 11/ 2011 opened a new era of targeted treatment for this disease. There are limited data on the "real-world" clinical experiences and outcomes of pts with MF treated in the JAK inhibitor era. MF became reportable to population-based cancer registries including the Surveillance, Epidemiology and End Results (SEER) program in 2001, making its investigation possible at the population level. The objective of this study was to assess the patterns of care and outcomes of older MF pts in the ruxolitinib era. Methods: Using the linked SEER-Medicare database, we identified a cohort of older pts diagnosed with MF from 2007 through 2015 who fulfilled the following eligibility criteria: 1) aged 66-99 years at diagnosis; 2) had known month of diagnosis; 3) were not identified from death certificate or autopsy only; 4) had continuous enrollment in Medicare Parts A, B and no enrollment in health maintenance organizations from 1 year before diagnosis until the end of follow-up (death or 12/31/2016, whichever came first); 5) had continuous enrollment in Medicare Part D from diagnosis until the end of follow-up; and 6) bone marrow biopsy claim from 1 year before diagnosis to end of follow up. Treatments were assessed via Medicare parts B&D claims. Kaplan-Meier curves and log-rank tests were used to compare survival between patient groups. Multivariable cox proportional hazards regression models were used to assess the effect of ruxolitinib use on survival in MF pts. Aside from treatment, we considered the influence of several characteristics on survival, including age at diagnosis, sex, race/ethnicity, marital status, comorbidities, SEER region and percentage living in poverty at the census tract level. Results: Among 528 MF pts, median age at diagnosis was 76 (interquartile range [IQR], 71- 80) years with 88.8% white and 56.1% male. 230 pts were diagnosed in the early era (2007-2011), and 298 in the late era (2012-2015), of which 113 (37.9%) were ruxolitinib users. There was no difference among any evaluated characteristics between two eras and by ruxolitinib status in the late era. The median duration of ruxolitinib use was 11.9 months. Similar number of pts started at 5, 10, 15 and 20 mg twice a day (BID) (Figure 1). Among 31 pts who started at ≤5 mg BID, 15 (48.4%) never had their dose of ruxolitinib escalated. While on ruxolitinib treatment, nearly half of the pts received additional medications for symptom management including hydroxyurea (22.6%), prednisone (17.9%) or both (10.4%). &lt; 11 users were able to go up to the highest dose of 25 mg BID. Ruxolitinib was interrupted &gt; 30 days for 31 times by 20 of 113 (17.7%) pts with median interruption duration of 43 (IQR 34-71) days. The median survival was 2.70 (95% confidence interval [CI]: 1.87-3.41) years and 2.62 (95% CI: 2.15-3.07) for the early and late era pts, respectively (p for log-rank 0.91). The multivariable analysis showed no impact of diagnosis era on survival (late vs early era hazard ratio (HR) of 1.08, 95% CI 0.83-1.40; p= 0.57). There was no difference in survival by ruxolitinib status (log-rank test, p=0.31), with a median survival of 2.76 (95% CI: 2.01-4.15) years and 2.53 (95% CI: 1.92-3.07) years among users and non-users, respectively (Figure 3). In the multivariable analysis, the risk of death among ruxolitinib users compared to non-users was not statistically significant with HR of 0.82 (95% CI 0. 59-1.16; p= 0.26). Conclusions: Older MF pts treated with ruxolitinib had similar survival when compared to pts who did not receive this medication, but the choice of ruxolitinib might have been influenced by disease risk which we were unable to assess. For many ruxolitinib users, the drug was interrupted, the dose was not escalated, additional medications were used concurrently (possibly to help control disease manifestation), and treatment was discontinued quickly after initiation. Optimization of ruxolitinib use may be necessary to accomplish better outcomes. Furthermore, development of new drugs which may be used together with ruxolitinib or after its discontinuation is needed. The work was supported by The Frederick A. Deluca Foundation. Disclosures Wang: Celgene/BMS: Research Funding. Ma:Celgene/BMS: Research Funding; BMS: Consultancy. Podoltsev:Jazz Pharmaceuticals: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Agios Pharmaceuticals: Consultancy, Honoraria; Sunesis Pharmaceuticals: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Blueprint Medicines: Consultancy, Honoraria; Bristol-Myers Squib: Consultancy, Honoraria; Genentech: Research Funding; AI Therapeutics: Research Funding; Samus Therapeutics: Research Funding; Astellas Pharma: Research Funding; Kartos Therapeutics: Research Funding; CTI biopharma: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Research Funding; Novartis: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Astex Pharmaceuticals: Research Funding; Daiichi Sankyo: Research Funding; Arog Pharmaceuticals: Research Funding.

scholarly journals Autologous Stem Cell Transplant Outcome in Classic Hodgkin Lymphoma Patients in the Era of Post-Transplant Brentuximab Vedotin Consolidation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3935-3935
Author(s):  
Shanee Chung ◽  
Jennifer White ◽  
Cynthia L. Toze ◽  
Heather J. Sutherland ◽  
David Sanford ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Salvage Chemotherapy ◽  
Brentuximab Vedotin ◽  
Relapse Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Classic Hodgkin Lymphoma

Abstract Introduction: Patients newly diagnosed with classic Hodgkin lymphoma (CHL) have over 80% chance of remission with first-line chemotherapy, such as ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regime. However, 10-40% of patients relapse eventually and require salvage therapy. High-dose therapy with autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed or refractory CHL, offering a cure rate of around 50%. This may be further improved to around 60% with post-transplant consolidation with brentuximab vedotin (BV). Post-SCT BV consolidation has been offered to all patients, regardless of the risk group, in British Columbia since late 2015. We set out to review the ASCT outcome in CHL patients in the recent decade at our institution. Methods: All adult patients who received ASCT for relapsed or refractory CHL between July 2011 and June 2020 were included in this retrospective analysis. Information pertaining to their demographics, disease characteristics, treatment history, transplant details, clinical outcomes and post-relapse therapy was obtained by review of electronic data. The data cut-off date was June 28, 2021. Survival outcomes were censored at the last known clinic visit for patients without relapse or death during follow up. Survival analysis was performed using Kaplan-Meier survival function and log-rank test. Pearson's chi-square test and ANOVA were used for comparison between cohorts. The statistical program used was Stata® version 16.1 (Texas, USA). Results: 114 patients underwent ASCT for relapsed/refractory CHL. Bulky disease and extranodal involvement were seen in 11% and 40% respectively at relapse. Looking at the 'high risk criteria' as defined in the AETHERA trial: 45/114 (40%) patients had primary refractory CHL, 21/114 (18%) had relapsed within 12 months of completing the front-line chemotherapy and 15/114 (13%) had relapsed beyond one year of completing initial treatment but with an extranodal disease. The most commonly used salvage chemotherapy regime was GDP (gemcitabine, dexamethasone, cisplatin; 111/114; 97%). 10/114 (9%) patients received BV after failing salvage chemotherapy pre-SCT. The median number of lines of therapy pre-SCT was two (range 2-5). 94/108 (98%) had a chemosensitive disease with 35/108 (32%) achieving complete remission. 6/108 (6%) patients had a progressive disease at the time of SCT. For the transplant, all patients had a peripheral blood stem cell source and the conditioning regime was either Carmustine/Etoposide/Cytarabine/Melphalan (76%) or Etoposide/Melphalan (24%). After median follow up of 62.2 months, 50/114 (44%) patients relapsed with median relapse-free survival of 20.2 months (range 0.9 - 113.5) and 16/114 (14%) died. The direct cause of death was lymphoma progression in all but three patients (PJP pneumonia, pulmonary fibrosis, traumatic subdural hematoma). Whereas only 4/51 (8%) patients (2 without relapse) received post-SCT BV consolidation via a compassionate access program between July 2011 and October 2015 (cohort 1), 45/63 (71%) patients (33 in remission) received routine BV consolidation between November 2015 and June 2020 (cohort 2). In cohort 2, 44% had primary refractory CHL compared to 33% in cohort 1 but the number of 'low risk' patients was similar at 29% (Table 1). The most common reason for no post-SCT BV consolidation in cohort 2 was patient refusal (7/18; 40%). Other causes included BV pre-SCT, early disease progression and patient comorbidities. Only 9/42 (21%) patients with available data in cohort 2 completed the planned 16 cycles of BV consolidation. The median number of cycles was 10.5 (range 1-16). The most common reasons for early termination of BV consolidation were peripheral neuropathy (22/33; 67%) and disease progression (9/33; 27%). There was no statistically significant difference in PFS or OS demonstrated between the two cohorts (Graphs 1, 2). Conclusion: After median follow up of 5 years, 86% of patients remain alive and 56% are alive in remission. In British Columbia, post-SCT BV consolidation has been widely adopted with over 70% of patients receiving at least one cycle since late 2015. Successful completion of post-SCT BV consolidation is, however, limited by a high rate of treatment-limiting peripheral neuropathy. Relapse-free survival benefit of routine post-SCT BV consolidation is not demonstrated in this single-centre cohort. Figure 1 Figure 1. Disclosures White: Novartis: Honoraria. Sutherland: Janssen: Consultancy, Research Funding; GSK: Research Funding; Karyopharm: Research Funding; Celgene: Consultancy; Amgen: Consultancy. Sanford: Abbvie: Membership on an entity's Board of Directors or advisory committees; Stellar: Membership on an entity's Board of Directors or advisory committees. Abou Mourad: Amgen: Consultancy; Paladin: Consultancy; Pfizer: Consultancy. Song: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Kite, a Gilead Company: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria.

scholarly journals Revesz syndrome revisited

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Michael Karremann ◽  
Eva Neumaier-Probst ◽  
Frank Schlichtenbrede ◽  
Fabian Beier ◽  
Tim H. Brümmendorf ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
English Literature ◽  
Bone Marrow Failure ◽  
Dyskeratosis Congenita ◽  
Kaplan Meier ◽  
Low Prevalence

Abstract Background Revesz syndrome (RS) is an extremely rare variant of dyskeratosis congenita (DKC) with only anecdotal reports in the literature. Methods To further characterize the typical features and natural course of the disease, we screened the English literature and summarized the clinical and epidemiological features of previously published RS cases. In addition, we herein describe the first recorded patient in central Europe. Results The literature review included 18 children. Clinical features are summarized, indicating a low prevalence of the classical DKC triad. All patients experienced early bone marrow failure, in most cases within the second year of life (median age 1.5 years; 95% CI 1.4–1.6). Retinopathy occurred typically between 6 and 18 months of age (median age 1.1 years; 95% CI 0.7–1.5). The incidence of seizures was low and was present in an estimated 20% of patients. The onset of seizures was exclusively during early childhood. The Kaplan–Meier estimate of survival was dismal (median survival 6.5 years; 95% CI 3.6–9.4), and none of the patients survived beyond the age of 12 years. Stem cell transplantation (SCT) was performed in eight children, and after a median of 22 months from SCT four of these patients were alive at the last follow up visit. Conclusion RS is a severe variant of DKC with early bone marrow failure and retinopathy in all patients. Survival is dismal, but stem cell transplantation may be performed successfully and might improve prognosis in the future.

Chromosomal Instability Correlates with Poor Outcome in Patients with Myelodysplastic Syndromes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5077-5077
Author(s):  
Christoph E. Heilig ◽  
Harald Löffler ◽  
Anna Jauch ◽  
Ulrich Mahlknecht ◽  
Anthony Ho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Disease Progression ◽  
Chromosomal Aberrations ◽  
Stable Disease ◽  
Myelodysplastic Syndromes ◽  
Chromosomal Instability ◽  
Sample Collection ◽  
Kaplan Meier ◽  
Blue Solid Line

Abstract Introduction: One of the hallmarks of human cancer is genomic instability, most often prevalent as chromosomal instability (CIN). CIN is defined by an elevated frequency of the occurrence of novel chromosomal aberrations and therefore, in contrast to aneuploidy, represents a rate rather than a state of genomic aberration. CIN has not only been implicated in the generation of aneuploidy, but also has been shown to play a pivotal role in both early malignant transformation and tumor progression. However, data on the presence and the extent of CIN in a defined population of primary malignant cells in different stages of disease are lacking. Myelodysplastic syndromes (MDS) are clonal stem-cell disorders characterized by ineffective hematopoiesis in one or more hematopoietic lineages and a high propensity for transformation into acute myeloid leukemia (AML). Furthermore, recurrent chromosomal aberrations are shared by both MDS and AML. Given their premalignant state, their frequent progression to AML, and their origin in an easy accessible stem-cell compartment, we considered MDS as a suitable model to study the role of CIN in tumor initiation and progression. Methods: We isolated CD34-positive cells from 18 patients with MDS, 30 patients with AML, 9 healthy controls, and 8 control patients with malignancies not involving the bone marrow. Patient samples were first objected to Ficoll density separation. Next, the CD34-positive cells were magnetically sorted (MACS) using CD34-microbeads. Purity of the sorted cells was controlled by flow cytometry (FACS) and constantly was greater 85%. Fluorescence in situ hybridization (FISH) was then performed, hybridizing centromeric probes for chromosomes 1, 6, 7, and 8, and subtelomeric probes for chromosomes 6 and 8 to the CD34-positive cells. Finally, the cell-to-cell variability of the chromosome content as well as the extent of structural instability was quantified by determining the modal signal number for each FISH probe and the median percentage of cells differing thereof. Results: In this study, we were able to identify a group of patients with numerical CIN values that were elevated more than two standard deviations relative to the mean of healthy control subjects (5.8% + 3.0%). This group of patients with elevated CIN values had a worse outcome as compared to the patients with normal CIN values: All three patients in the ‘high CIN’ group reached the endpoint, defined as progression to AML (two patients) or death (one patient), within 4.9, 10.2, and 12.3 months after sample collection, respectively, whereas among the remaining 15 patients with normal CIN values there was only one case of death (3.9 months after sample collection) and one patient with progression to AML (20.1 months after sample collection) at a median follow-up of 14.2 months (Figure 1). Furthermore, we were able to demonstrate an increase of CIN preceding the transformation to AML in one patient with MDS RAEB-2 over the course of five months. Eventually, our results neither did indicate a role for structural CIN in MDS disease progression, nor did they show a difference between clinically defined subgroups, indicating that CIN may represent a novel prognostic marker independent of the conventional classification criteria for MDS. Conclusion: Our data indicate a possible role for numerical CIN in the progression of MDS to AML. Moreover, a CD34-positive cell-specific increase of CIN might be a predictor for the subsequent disease progression to AML. Therefore, the quantification of CIN in hematopoietic progenitor cells might be valuable for identifying patients with high-risk MDS more reliably. Figure 1: Kaplan-Meier-Plot comparing the outcome of MDS patients with elevated CIN values (red dashed line) and normal CIN values (blue solid line). After a median follow-up of 14.2 months, all but two patients in the “low CIN” group had stable disease, whereas all three patients with elevated CIN values reached the endpoint, defined as progression to AML or death. Figure 1:. Kaplan-Meier-Plot comparing the outcome of MDS patients with elevated CIN values (red dashed line) and normal CIN values (blue solid line). After a median follow-up of 14.2 months, all but two patients in the “low CIN” group had stable disease, whereas all three patients with elevated CIN values reached the endpoint, defined as progression to AML or death.

Sign in / Sign up

Export Citation Format

Share Document