Outcome of Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia (ALL) By Age Group over 35 Years: A Single Institution Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3975-3975 ◽  
Author(s):  
Koji Sasaki ◽  
Elias J. Jabbour ◽  
Susan M. O'Brien ◽  
Deborah A Thomas ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Age Groups ◽  
Advisory Board ◽  
Time Interval ◽  
Age Group ◽  
Hematopoietic Stem ◽  
Age Cohorts ◽  
The Impact

Abstract Background: The incorporation of intensive chemotherapy, hematopoietic stem cell transplantation (HSCT), targeted therapies including rituximab and tyrosine kinase inhibitors contributes substantial improvement in the outcome of patients with ALL over decades. VAD was changed to hyper-CVAD in 1992; rituximab was added to hyper-CVAD for CD20 positive ALL in 1999/2000; inotuzumab ozogamicin in combination with low-intensity chemotherapy was offered to elderly patients starting in 2011. The aim of this study is to describe the outcome of patients with ALL over decades by age groups. Methods: From 1980 to 2016, patients with newly diagnosed ALL at our institution were analyzed. Burkitt leukemia was excluded from our analysis. Patients were divided into age groups as follows: age 15-39, age 40-60, and age >60. Patients were subsequently divided into diagnostic year cohorts by decade: 1980-1989, 1990-1999, 2000-2009, and 2010-2016. Overall survival was defined as time interval from diagnosis to the date of death regardless of any cause. Kaplan-Meier method with a log-rank test was used for survival comparison between cohorts. Stepwise multivariate analysis with Cox proportional hazards model was used to evaluate the impact of diagnosis year on OS. P-values were two-sided, and a p-value less than 0.05 was considered statistically significant. Results: Overall, 972 patients were identified and analyzed in our study. Median age at diagnosis was 39.5 years (range, 16-92) with a median follow-up of 10.4 years (range, 0.0-31.3). Patients were divided into 486 patients (50%) in the age 15-39 category, 301 patients (31%) in the age 40-60 category, and 185 patients (19%) in the age over 60 category. Baseline patient characteristics are summarized in Table 1. Overall, the median OS durations were 4.5 years, 2.8 years, and 1.3 years in age 15-39, age 40-60, and age >60, respectively (p<0.001; p<0.001). Of the 486 patients in age 15-39, the improvement in OS was observed from 1980-1989 to 1990-1999 (p<0.001); of the 301 patients in age 40-60, from 1980-1989 to 1990-1999, and from 1990-1999 to 2000-2009 (p=0.042; p=0.003); of the 185 patients in age >60, from 2000-2009 to 2010-2016 (p=0.039). Stepwise multivariate analysis identified leukocytosis, thrombocytopenia, hypoalbuminemia, elderly age, poor performance status, lack of complete response, and diagnostic year as adverse prognostic factors for OS. Each year since 1980 had an impact on OS with hazard ratio of 0.961 (95% confidence interval, 0.951-0.971; p<0.001). Conclusion: Patients with ALL have significant improvement in OS throughout all ages over decades. However, the decade time points of improvement in OS were different between age cohorts. Different treatment strategy and clinical trial designs by each age group are needed for further improvement in patient's outcome. Disclosures Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. O'Brien:Janssen: Consultancy, Honoraria; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding. Ravandi:BMS: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Wierda:Novartis: Research Funding; Abbvie: Research Funding; Acerta: Research Funding; Gilead: Research Funding; Genentech: Research Funding. Konopleva:Cellectis: Research Funding; Calithera: Research Funding. Pemmaraju:incyte: Consultancy, Honoraria, Research Funding; novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria; stemline: Consultancy, Honoraria, Research Funding; cellectis: Consultancy, Research Funding; affymetrix: Research Funding. DiNardo:Agios: Other: advisory board, Research Funding; Daiichi Sankyo: Other: advisory board, Research Funding; Celgene: Research Funding; Abbvie: Research Funding; Novartis: Other: advisory board, Research Funding. Jain:Genentech: Research Funding; Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Novimmune: Consultancy, Honoraria; Seattle Genetics: Research Funding; Abbvie: Research Funding; Servier: Consultancy, Honoraria; Celgene: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Infinity: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding. Andreeff:Oncoceutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Use of First or Second Generation TKI for CML after Allogeneic Stem Cell Transplantation: a Study By the CMWP of the EBMT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4685-4685 ◽  
Author(s):  
Yves Chalandon ◽  
Simona Iacobelli ◽  
Jennifer Hoek ◽  
Linda Koster ◽  
Liisa Volin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Chronic Phase ◽  
Time Interval ◽  
Hematopoietic Stem ◽  
Persistent Disease ◽  
Factors Influencing

Abstract Background: Patients (pts) relapsing with CML after allogeneic hematopoietic stem cell transplantation (alloHSCT) may be treated with tyrosine kinase inhibitors (TKI) and/or donor lymphocyte infusions (DLI). As nowadays the majority of CML patients would have received at least imatinib prior to transplantation, we were interested in analizing a) the type of TKI used after alloHSCT, b) the indication for TKI treatment, c) the outcome of this treatment and d) the temporal relationship with DLI if given. Patients and methods: 435 pts received TKI after first allogeneic HSCT for CML for different reasons. Transplants had been performed in first chronic phase (CP1, n=194), accelerated phase (AP, n= 60) or for more advanced disease (blast crisis (BC)/> CP1, n=177) from HLA identical siblings (n=231) or unrelated donors (n=204) between 2000 and 2013. TKI given prior to transplant was imatinib (n=268), dasatinib (n=162), nilotinib (n=88), bosutinib (n=4) and ponatinib (n=7). Median age at transplant was 44 (18.5-68) years, 274 pts (63%) were male. TKI post alloHSCT were given between 2000 and 2015. 1st TKI given was either imatinib (n=223), dasatinib (n=131), nilotinib (n=67), bosutinib (n=2) or ponatinib (12). The indications for TKI therapy were the same as for transplantation (n=262), for relapse/progression/persistent disease (n=124), for prophylaxis/pre-emptive (n=32), planned (n=5), others (n=8) and missing (n=4). Results: Median follow-up from start of TKI was 55 (1-171) months. The median time interval from transplant to TKI was 6 (0.2-165) months. It was longer for TKI given for relapse/progression with 15 (1-89) months and shorter for TKI given for prophylaxis/pre-emptive with 1.6 (0.2-43) months. It was longer for imatinib with 11 (0.2-121) months vs 3.8 (0.2-165) months for other TKI. Imatinib as 1st TKI was mainly given for relapse/progression/persistent disease (48%) and the other TKI for the same reason as for transplantation (83%). 103/223 (46%) of pts with imatinib, 99/131 (76%) with dasatinib, 55/67 (82%) with nilotinib and 11/14 (79%) with bosutinib/ponatinib post-transplantation had been treated with imatinib prior to transplantation. In total, 196 (45%) patients received DLI after alloHSCT, of which 63/435 (14.5%) had DLI prior to TKI post-alloHSCT, 19/435 (4.4%) had DLI at the same time of TKI and 114/435 (26%) had DLI post-TKI. Best response after TKI was complete molecular remission in 17.7%, cytogenetic remission in 4.4%, hematological remission in 20.2% and no response/progression/relapse in 57.7% of pts. 50% of pts treated with imatinib had a response (molecular/cytogenetic/hematological) vs 34% with nilotinib, 33% with dasatinib and 33% with bosutinib/ponatinib, p=0.014. OS was 60% (55-65%) at 5 years. It was 66% (60-73%) with imatinib vs 51% (42-60%) with other TKI, p=0.0024. 5 years RFS was 47% (42-53%). It was 53% (46-60%) with imatinib vs 40% (32-48%) with other TKI, p=0.0102. 5 years RI was 25% (21-30%). It was 21% (16-27%) with imatinib vs 31% (24-38%) with other TKI, p=0.0454. 5 years NRM was 27% (23-32%). It was 26% (20-31%) with imatinib vs 29% (22-36%) with other TKI, p=0.365. In multivariate analysis for OS, imatinib vs other TKI post-transplant did not show anymore an effect, HR 1.19 (0.85-1.67), p=0.317. Factors influencing OS were time from diagnosis to transplant, HR 1.01 (1.00-1.01), p=0.009, AP vs CP1, HR 1.80 (1.11-2.91), p=0.017 and BC/>CP1 vs CP1, HR 2.3 (1.58-3.33), p<0.0001. In multivariate analysis for RFS as for OS, imatinib vs other TKI did not have an effect, HR 1.11 (0.83-1.48), p=0.496. Other factors having a tendency or influencing RFS were time from diagnosis to transplant, HR 1.00 (1.00-1.01), p=0.054, AP vs CP1, HR 1.52 (1.00-2.31), p=0.050 and BC/>CP1 vs CP1, HR 2.11 (1.55-2.88), p<0.001. Conclusion: These data suggest that TKI after alloHSCT induce a response in about 42% of pts regardless of the type of TKI used and that time from diagnosis to transplantation as well as the phase of disease at transplant remain the main factors influencing the outcome of CML patients relapsing after alloHSCT. Disclosures Kröger: Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding.

scholarly journals Association between Sociodemographic, Clinical and Immunophenotypic Variables with Disease Relapse and Survival at 12 Months, in Patients with B-Cell Acute Lymphoblastic Leukemia Treated at a Colombian University Hospital

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4380-4380
Author(s):  
Luis Antonio Salazar ◽  
Sandra Vanesa Rios ◽  
Angela María Peña ◽  
Maria Luna-Gonzalez ◽  
Mario Andrés Arenas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Survival Function ◽  
Advisory Board ◽  
Overweight And Obesity ◽  
University Hospital ◽  
The Impact

Abstract INTRODUCTION Acute lymphoblastic leukemia (ALL) is a clonal hematopoietic disorder that originates from B or T lymphoid progenitors. It affects more frequently children, but prognosis is worse in adults. ALL has a high incidence in Hispanics (Swords R et al. Blood Cancer J. 2016) and is important to identify baseline clinical, sociodemographic, and cytogenetic characteristics in these patients that are relevant for relapse free and overall survival. Reports of Hispanic patients with ALL outsides of the U.S.A are scare but are important to further characterize the impact of this disease in minority populations. OBJETIVE To describe the association between sociodemographic, clinical and immunophenotypic variables with 12-month relapse free survival (RFS) and overall survival (OS) in patients diagnosed and treated for ALL in a Colombian university hospital (FOSCAL). MATERIALS AND METHODS This is a descriptive observational cohort study that included patients older than 18 years with a confirmed diagnosis of ALL treated in a tertiary university hospital between 2013-2020 and that had at least 12 months follow-up after starting treatment. Baseline sociodemographic, clinical, laboratory and immunophenotypic data were collected. Bivariate analyses of both relapse and mortality cumulative incidences at 12 months, with relative risks (RR) and their 95% Confidence intervals were performed, using either chi-square or Fischer exact test when needed. In a second term, bivariate survival analyses through Kaplan-Meier survival function and Hazard ratios were evaluated, using Cox proportional hazards as the main statistical test. RESULTS Among 128 of include patients, the median age at diagnosis was 34 years (range 0-89 years), 54% were men, 6.2% had type 2 Diabetes Mellitus (T2DM), most had an ECOG PS of 0 (72.7%), 31.8% had splenomegaly, 12% had hepatomegaly and 47% presented without organomegalies. The proportion of patients with overweight and obesity were 26.3% and 22.2% respectively. At diagnosis 80.5% and 8.8% of patients had high risk and standard risk ALL, respectively Forty-eight patients had a FAB classification with 58% being ALL-2 and most of the were unclassified. Most cases (81%) had B-cell immunophenotype, with 55% being pre-B-cell and 32% mature B-cell. Twelve percent of patients were Ph+ B-ALL. At 12 months, the proportion of mortality was 34.4%. Most of the patients (83%) did not have major co-morbidities, however patients with T2DM had a significantly inferior survival at 12 months, HR: 3.68 (95%CI 1.54-8.8 P=0.003), as patients older than 35 years (HR: 2.15, 95%CI: 1.14-4.0, P=0.017) (Table 1). CONCLUSIONS Colombian patients with B-cell ALL have similar clinical, immunophenotypic and cytogenetic (Ph+ prevalence) characteristics as seen in other international cohorts. In our cohort patients older than 35 years and subjects with T2DM had inferior survival at 1 year. Further analyses of socioeconomic factors, molecular features and response to specific regimens are needed to have a better understanding of Colombian B-ALL patients. Figure 1 Figure 1. Disclosures Salazar: Amgen: Research Funding. Peña: Amgen: Research Funding. Sandoval-Sus: BMS: Other: Advisory Board, Speakers Bureau; SeaGen, Janssen, MassiveBio, TG: Other: Advisory Board. Sossa: Amgen: Research Funding.

Age Differences in Disease Characteristics, Patterns of Care, and Outcomes of Follicular Lymphoma (FL) in the United States (US): Report From the National Lymphocare Study (NLCS)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3708-3708
Author(s):  
Chadi Nabhan ◽  
Michelle Byrtek ◽  
Shadi Latta ◽  
Keith L Dawson ◽  
Xiaolei Zhou ◽  
...  
Keyword(s):  
Research Funding ◽  
Age Groups ◽  
Age Group ◽  
Employment Equity ◽  
Disease Characteristics ◽  
Baseline Factors ◽  
Equity Ownership ◽  
Grade 3 ◽  
The Impact ◽  
To Receive

Abstract Abstract 3708 Background: There are few prospective studies on disease characteristics, patterns of care, response, and outcomes in elderly FL patients (pts) in the US. The NLCS is a Genentech-sponsored prospective multicenter registry study that collects this information without study-specific treatment. We utilized the NLCS database to better understand the impact of age on FL outcome. Patients and Methods: All evaluable pts with FL histology in the NLCS were included except pts with FL plus other lymphoma histology or pts who progressed before first treatment or before being assigned to watchful waiting (WW). Using Pearson Chi-Square tests, associations of age groups (≤60, 61–70, >70) with disease characteristics and overall response (ORR) were examined. Median PFS and OS by treatment regimen were estimated using Kaplan-Meier methods for each age group. Cox proportional hazards regression adjusted for baseline factors (grade, number of nodal sites, LDH, Hgb, stage, performance status (PS), bone marrow (BM) involvement, race, and treatment center type) were used to assess treatment differences in PFS and OS and the significance of age by treatment interactions. Results: Of 2,647 pts, 47% (n=1,254) were ≤60 yrs, 25% (n=666) were 61–70 yrs, and 27% (n=727) were >70 yrs (min age of 22; max of 97). Compared with pts ≤60 yrs, pts 61–70 and >70 were more likely to be white (93% >70, 92% 61–70, and 88% ≤60, P=.02 and .02 respectively), have stage I/II disease (37% >70, 36% 61–70, and 29% ≤60, P=.0008 and .0003), have <5 nodal sites (73% >70, 69% 61–70, and 61% ≤60, P=.001 and <.0001), and have poor-risk FLIPI (53% >70, 51% 61–70, and 15% ≤60, P<.0001 and <.0001). Compared with pts ≤60, elderly pts (>70) were more likely to have FL grade 3 (24% vs 18%, P=.01). While there were no differences in geographic distribution by age, elderly pts were more likely to receive therapy at community practices (86%) versus academic institutions than pts ≤60 (77%, P<.0001) or 61–70 (81%, P=.004). Treatments varied significantly by age (P<.0001). More elderly pts were observed compared to pts ≤60 (23% vs19%). When treated, elderly pts (22%) were more likely to receive rituximab (R) monotherapy compared with patients aged 61–70 (12%) or ≤60 (10%). When chemotherapy alone or plus R was given, elderly pts were less likely to receive anthracyclines (45% vs 65% (61–70) and 68% (≤60)). Among all variables, only grade 3 histology predicted anthracycline use in all age groups. Lack of BM involvement predicted anthracycline use for younger pts (≤60 and 61–70). Of those ≤60, white pts were more likely to receive anthracyclines, and of those 61–70, those with ≥5 nodal sites were more likely to receive anthracyclines. ORRs were similar across age groups receiving similar regimens with R plus chemo providing the highest ORR. Adjusting for baseline factors, treatment (WW, R, R-Chemo, or other) benefit varied for each age group in terms of PFS (P=.02), with treatment outcomes being most differentiated among younger pts (Table). PFS appeared shorter in elderly pts regardless of the treatment received. No significant interaction between age and efficacy of anthracycline in terms of PFS or OS was observed (P-values >.65), but the overall effect of anthracycline for all pts was beneficial for PFS (HR=0.80, P=.02) and OS (HR=0.67, P=.003). Median OS was 8 years for elderly and not reached for others. After adjusting for baseline factors, no significant differences in treatment impact by age on OS were seen. Elevated LDH, reduced Hgb, stage III/IV, PS ≥1, and BM involvement were all significantly associated with shortened OS. These factors were also significantly associated with treatment choice, as worse-prognosis elderly pts were more likely to receive either R or R+chemo than WW or other treatment. Conclusions: FL pts >70 yrs more commonly received R alone and less commonly received anthracyclines when treated with chemotherapy. The impact of anthracyclines on PFS did not vary by age, but differences in PFS for other treatment regimens showed a stronger association among younger pts Disclosures: Nabhan: Genentech: Research Funding, Speakers Bureau. Byrtek:Genentech, Inc., a member of the Riche Group: Employment, Equity Ownership. Dawson:Genentech, Inc., a member of the Riche Group: Employment, Equity Ownership. Link:Genentech, Inc., a member of the Riche Group: Consultancy; Celgene: Consultancy; Spectrum: Consultancy. Friedberg:Genentech: Consultancy. Cerhan:Genentech: National LymphoCare Scientific Advisory Board Other. Flowers:Celgene: Consultancy; Prescription Solutions: Consultancy; Seattle Genetics: Consultancy; Millennium: Consultancy, Research Funding; Genentech: Consultancy; GIlead: Research Funding; Spectrum: Research Funding; Janssen: Research Funding; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees.

Biologic Features and Treatment Outcome of Secondary Acute Lymphoblastic Leukemia - Review of 101 Cases.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4345-4345
Author(s):  
Ranga Shivakumar ◽  
Wei Tan ◽  
Gregory Wilding ◽  
Eunice S. Wang ◽  
Meir Wetzler
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Age Groups ◽  
Primary Diagnosis ◽  
Initial Diagnosis ◽  
Older Age ◽  
Time Interval ◽  
Age Group ◽  
Complex Karyotype ◽  
Old Patients

Abstract Secondary acute lymphoblastic leukemia (sALL) is a rare disease and its biologic features are not well described. Data suggested that sALL occurs more frequently at older age. Since leukemia at older age in general is associated with worse outcome, we wanted to assess the biology and outcome of patients with sALL by age at time of primary diagnosis. We describe a cohort of 7 patients and found additional 94 cases in the literature on whom biological parameters were described. Patients were stratified (at least 5 patients per strata) according to their age at initial diagnosis (<18, 18–59, and ≥60 years of age), initial diagnosis [acute myeloid leukemia (AML), Hodgkin’s disease (HD), neuroblastoma, breast and prostate cancers], cytogenetic groups [diploid, t(9;22), 11q23 aberrations, complex karyotype], immunophenotypes (B vs. T), and Burkitt’s defined by either morphology and/or cytogenetic analysis demonstrating c-myc rearrangement. A total of 101 patients were evaluated; 29 were <18, 54 were 18–59 and 18 were ≥60 years old. The distribution of primary diagnoses was as expected: neuroblastoma was seen only in the <18 age group (P=0.003), HD was more common in the 18–59 age group (75% of all HD cases; P=0.084) while breast (P=0.003) and prostate (P=0.005) cancers were prevalent only in the >18 year old patients. The time interval to develop sALL was similar among the three age groups (3, 2.2 and 1.8 years, P=0.561). However, the time interval to develop sALL was longer for HD (5.5 years) and neuroblastoma (3.7 years) as compared to AML (1 year), breast (1.6 years) and prostate (1.98 years) cancers (overall P=0.0003). Further, the time interval to develop sALL was significantly longer for patients with complex karyotype (5.3 years) as compared to all other aberrations [11q23 − 1.78; t(9;22) − 1.9; diploid − 1.98 years; overall P=0.0497]. Disease characteristics at diagnosis were as follows: T cell immunophenotype was more common in the <18 age group (P=0.016) and the presence of 11q23, t(9;22), complex and normal karyotypes was equally distributed among the three age groups (P=0.2, 0.073, 0.635 and 0.271 individually). Complete remission was infrequent in the ≥60 age group (22.22%) compared to the other groups (73.9% for <18 and 67.7% for 18–59; P=0.025). Even though only patients <60 years old were transplanted (33.3% for <18 and 19.4% for 18–59; P=0.102), the overall survival was poor in all age groups [probability of survival at 1 year for <18=0.222, 18–59=0.226 and ≥60=0.3 (P=0.7941)]. Primary diagnoses, cytogenetic subgroups and immunophenotype did not affect outcome. In summary, the time interval to develop sALL is significantly longer for HD, neuroblastoma and complex karyotype. However, sALL is associated with very poor outcome regardless of age and any of the biologic features. Therefore, identification of prognostic factors to prevent the occurrence of sALL is needed.

scholarly journals Impact of Renal Dysfunction Measured By Estimated Glomerular Filtration Rate (eGFR) on Outcomes after Allogeneic Hematopoietic Cell Transplantation (HCT)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3256-3256
Author(s):  
Nosha Farhadfar ◽  
Ajoy L. Dias ◽  
Tao Wang ◽  
Caitrin Fretham ◽  
Hemant S. Murthy ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Renal Dysfunction ◽  
Research Funding ◽  
Large Population ◽  
Advisory Board ◽  
One Year ◽  
Analysis Models ◽  
The Impact ◽  
Overall Mortality

Introduction Renal dysfunction is a recognized risk factor for mortality after HCT, as it is included in the comorbidity index (HCT CI). Yet, further understanding on outcomes in patients with different level of renal dysfunction or undergoing hemodialysis (HD) at time of transplant remains scant. This study explores the impact of different levels renal dysfunction on major HCT outcomes in a large population using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Methods The study population included 8,102 patients age 40 years and older who received HCT for treatment of malignancies from 2008 to 2016, with available pre-transplant creatinine measurement. eGFR, calculated using CKD-EPI (CKD-epidemiology collaboration) method, was used to assigned patients in four categories: eGFR ≥ 90ml/min (eGFR≥ 90, N=4,237, reference), eGFR 60-90ml/min (eGFR 60-90, N=3,158), eGFR 45-59ml/min (eGFR 45-59, N=538) and eGFR <45ml/min(eGFR<45, N=169). A separate cohort of patients on HD at time of HCT (N=46) was analyzed independently. Multivariate analysis models were built for assessment of overall mortality, transplant-related mortality (TRM), disease relapse or progression, graft-versus-host disease (GVHD), hepatic sinusoidal obstructive syndrome (SOS), thrombotic microangiopathy (TMA), idiopathic pneumonia syndrome (IPS) and need of HD post-transplant. Common patient-, disease- and transplant-related covariates were tested on all models and HCT CI was computed without reported renal dysfunction comorbidity to avoid collinearity. Results Patient characteristics are shown in table 1. The groups were comparable on disease risk index, graft and donor source, but patients with eGFR>90 were younger and received myeloablative conditioning more frequently. The cohort of eGFR <45 had a higher proportion of patients with HCT CI ≥3. TRM and overall survival according to eGFR groups are shown in Figure. In the multivariate analysis models eGFR as the main effect was associated with TRM (p<0.0001), overall mortality (p<0.0001), and requirement of HD post HCT (p<0.0001), but not for relapse/progression (p=0.98), GVHD (grades II-IV, p=0.34; III-IV, p=0.70; and chronic, p=0.20), TMA (p=0.46), SOS (p=0.02) or IPS (p=0.06). Compared to eGFR ≥90, the hazard ratio (HR) for TRM for eGFR 60-89 was 1.12 (p=0.07), for eGFR 45-59 was 1.46 (p<0.001) and for eGFR<45 was 1.74 (p=0.004). Corresponding HRs for overall mortality were 1.0 (p=0.9), 1.17 (p=0.03) and 1.63 (p<0.0001), respectively. Similarly, for the need of HD post HCT, HR for eGFR60-89 was 1.29 (p=0.03), eGFR45-59 was 2.45 (p<0.001) and for eGFR<45 was 3.09 (p<0.0001). Only eGFR<45 was associated with higher risk of SOS (HR2.66, p=0.03). Among 46 patients on HD prior to HCT, one-year probability of overall survival was 20% (95% Confidence Interval [CI] 10-32%) and cumulative incidence of TRM at one year was 67% (95% CI, 50-81%). Conclusion These findings indicate that degree of renal dysfunction is an independent predictor of OS, TRM, probability of receiving HD and SOS when adjusted for other risk factors. The impact of eGFR on the need of HD, a complication that increases morbidity post HCT is an important finding. Additionally, the outcomes of a subset of patients on HD at time of transplants are dismal. These results can further assist the prognostic assessment of candidates for an allogeneic HCT. Disclosures Stadtmauer: Celgene: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Novartis: Consultancy, Research Funding; Tmunity: Research Funding; Abbvie: Research Funding. Wingard:Ansun: Consultancy; Pluristem: Consultancy; Celgene: Consultancy; Merck: Consultancy; Shire: Consultancy. Ganguly:Seattle Genetics: Speakers Bureau; Daiichi Sankyo: Research Funding; Kite Pharma: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board. Pasquini:Pfizer: Other: Advisory Board; Amgen: Consultancy; Medigene: Consultancy; BMS: Research Funding; Novartis: Research Funding; Kit Pharma: Research Funding.

scholarly journals Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jaime Sanz ◽  
Jacques-Emmanuel Galimard ◽  
Myriam Labopin ◽  
Boris Afanasyev ◽  
Moiseev Ivan Sergeevich ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cumulative Incidence ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Donor Type ◽  
Matched Sibling ◽  
The Impact

Abstract Background There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.

scholarly journals Family history of early onset acute lymphoblastic leukemia is suggesting genetic associations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinjun Li ◽  
Kristina Sundquist ◽  
Jan Sundquist ◽  
Asta Försti ◽  
Kari Hemminki
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Statistical Significance ◽  
Age Groups ◽  
Age Group ◽  
Genetic Associations ◽  
Sequencing Data ◽  
Cancer Data ◽  
Group 5 ◽  
Prostate Cancers

AbstractChildhood acute lymphoblastic leukemia (ALL) has an origin in the fetal period which may distinguish it from ALL diagnosed later in life. We wanted to test whether familial risks differ in ALL diagnosed in the very early childhood from ALL diagnosed later. The Swedish nation-wide family-cancer data were used until year 2016 to calculate standardized incidence ratios (SIRs) for familial risks in ALL in three diagnostic age-groups: 0–4, 5–34 and 35 + years. Among 1335 ALL patients diagnosed before age 5, familial risks were increased for esophageal (4.78), breast (1.42), prostate (1.40) and connective tissue (2.97) cancers and leukemia (2.51, ALL 7.81). In age-group 5–34 years, rectal (1.73) and endometrial (2.40) cancer, myeloma (2.25) and leukemia (2.00, ALL 4.60) reached statistical significance. In the oldest age-group, the only association was with Hodgkin lymphoma (3.42). Diagnostic ages of family members of ALL patients were significantly lower compared to these cancers in the population for breast, prostate and rectal cancers. The patterns of increased familial cancers suggest that BRCA2 mutations could contribute to associations of ALL with breast and prostate cancers, and mismatch gene PMS2 mutations with rectal and endometrial cancers. Future DNA sequencing data will be a test for these familial predictions.

scholarly journals Infant Acute Myeloid Leukemia: A Unique Clinical and Biological Entity

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 777
Author(s):  
Charlotte Calvo ◽  
Odile Fenneteau ◽  
Guy Leverger ◽  
Arnaud Petit ◽  
André Baruchel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Age Groups ◽  
Study Groups ◽  
Biological Entity ◽  
Age Group ◽  
Older Children ◽  
Megakaryoblastic Leukemia ◽  
Acute Myeloid

Infant acute myeloid leukemia (AML) is a rare subgroup of AML of children <2 years of age. It is as frequent as infant acute lymphoblastic leukemia (ALL) but not clearly distinguished by study groups. However, infant AML demonstrates peculiar clinical and biological characteristics, and its prognosis differs from AML in older children. Acute megakaryoblastic leukemia (AMKL) is very frequent in this age group and has raised growing interest. Thus, AMKL is a dominant topic in this review. Recent genomic sequencing has contributed to our understanding of infant AML. These data demonstrated striking features of infant AML: fusion genes are able to induce AML transformation without additional cooperation, and unlike AML in older age groups there is a paucity of associated mutations. Mice modeling of these fusions showed the essential role of ontogeny in the infant leukemia phenotype compared to older children and adults. Understanding leukemogenesis may help in developing new targeted treatments to improve outcomes that are often very poor in this age group. A specific diagnostic and therapeutic approach for this age group should be investigated.

scholarly journals Treatment Patterns and Outcomes in Elderly Patients with Newly Diagnosed Multiple Myeloma: Results from the Connect® MM Registry

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3129-3129
Author(s):  
Hans C. Lee ◽  
Sikander Ailawadhi ◽  
Cristina Gasparetto ◽  
Sundar Jagannath ◽  
Robert M. Rifkin ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Causes Of Death ◽  
Age Groups ◽  
Treatment Patterns ◽  
Age Group ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Background: Multiple myeloma (MM) is common among the elderly, with 35% of patients (pts) diagnosed being aged ≥75 years (y). With increasing overall life expectancy, the incidence and prevalence of newly diagnosed and previously treated MM patients ≥80 y is expected to increase over time. Because elderly pts are often excluded from clinical trials, data focused on their treatment patterns and clinical outcomes are lacking. The Connect® MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed MM (NDMM) designed to examine real-world diagnostic patterns, treatment patterns, clinical outcomes, and health-related quality of life patient-reported outcomes. This analysis reviews treatment patterns and outcomes in elderly pts from the Connect MM Registry. Methods: Pts enrolled in the Connect MM registry at 250 community, academic, and government sites were included in this analysis. Eligible pts were adults aged ≥18 y with symptomatic MM diagnosed ≤2 months before enrollment, as defined by International Myeloma Working Group criteria; no exclusion criteria were applied. For this analysis, pts were categorized into 4 age groups: <65, 65 to 74, 75 to 84, and ≥85 y. Pts were followed from time of enrollment to the earliest of disease progression (or death), loss to follow-up, or data cutoff date of February 7, 2019. Descriptive statistics were used for baseline characteristics and treatment regimens. Survival outcomes were analyzed using Cox regression. Time to progression (TTP) analysis excluded causes of death not related to MM. Results: Of 3011 pts enrolled (median age 67 y), 132 (4%) were aged ≥85 y, and 615 (20%) were aged 75-84 y at baseline. More pts aged ≥85 y had poor prognostic factors such as ISS stage III disease and reduced hemoglobin (<10 g/dL or >2 g/dL <LLN) compared with other age groups, although no notable differences between creatinine and calcium levels were observed across age groups (Table). A lower proportion of elderly pts (75-84 and ≥85 y) received triplet regimens as frontline therapy. More elderly pts received a single novel agent, whereas use of 2 novel agents was more common in younger pts (Table). The most common frontline regimens among elderly pts were bortezomib (V) + dexamethasone (D), followed by lenalidomide (R) + D, whereas those among younger pts included RVD, followed by VD and CyBorD (Table). No pt aged ≥85 y, and 4% of pts aged 75-84 y received high-dose chemotherapy and autologous stem cell transplant (vs 61% in the <65 y and 37% in the 65-74 y age group). The most common maintenance therapy was RD in pts ≥85 y (although the use was low) and R alone in other age groups (Table). In the ≥85 y group, 27%, 10%, and 4% of pts entered 2L, 3L, and 4L treatments respectively, vs 43%, 23%, and 13% in the <65 y group. Progression-free survival was significantly shorter in the ≥85 y age group vs the 75-84 y age group (P=0.003), 65-74 y age group (P<0.001), and <65 y age group (P<0.001; Fig.1). TTP was significantly shorter in the ≥85 y group vs the <65 y group (P=0.020); however, TTP was similar among the 65-74 y, 75-84 y, and ≥85 y cohorts (Fig. 2). Overall survival was significantly shorter in the ≥85 y group vs the 75-84 y, 65-74 y, and <65 y groups (all P<0.001; Fig. 3). The mortality rate was lowest (46%) during first-line treatment (1L) in pts aged ≥85 y (mainly attributed to MM progression) and increased in 2L and 3L (47% and 54%, respectively); a similar trend was observed in the younger age groups. The main cause of death was MM progression (29% in the ≥85 y vs 16% in the <65 y group). Other notable causes of death in the ≥85 y group included cardiac failure (5% vs 2% in <65 y group) and pneumonia (5% vs 1% in <65 y group). Conclusions: In this analysis, elderly pts received similar types of frontline and maintenance regimens as younger pts, although proportions varied with decreased use of triplet regimens with age. Considering similarities in TTP across the 65-74 y, 75-84 y, and ≥85 y cohorts, these real-world data support active treatment and aggressive supportive care of elderly symptomatic pts, including with novel agents. Additionally, further clinical studies specific to elderly patients with MM should be explored. Disclosures Lee: Amgen: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ailawadhi:Janssen: Consultancy, Research Funding; Takeda: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Cellectar: Research Funding. Gasparetto:Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Jagannath:AbbVie: Consultancy; Merck & Co.: Consultancy; Bristol-Myers Squibb: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy. Rifkin:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Narang:Celgene: Speakers Bureau. Terebelo:Celgene: Honoraria; Jannsen: Speakers Bureau; Newland Medical Asociates: Employment. Toomey:Celgene: Consultancy. Hardin:Celgene: Membership on an entity's Board of Directors or advisory committees. Wagner:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Cancer Society: Other: Section editor, Cancer journal. Omel:Celgene, Takeda, Janssen: Other: Patient Advisory Committees. Srinivasan:Celgene: Employment, Equity Ownership. Liu:TechData: Consultancy. Dhalla:Celgene: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Abonour:BMS: Consultancy; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

scholarly journals Vaccine impact and effectiveness of meningococcal serogroup ACWY conjugate vaccine implementation in the Netherlands: a nationwide surveillance study

2021 ◽  
Author(s):  
Milou Ohm ◽  
Susan J M Hahné ◽  
Arie van der Ende ◽  
Elizabeth A M Sanders ◽  
Guy A M Berbers ◽  
...  
Keyword(s):  
The Netherlands ◽  
Incidence Rate ◽  
Vaccination Programme ◽  
Screening Method ◽  
Age Groups ◽  
Incidence Rates ◽  
Age Group ◽  
Mass Campaign ◽  
Conjugate Vaccination ◽  
The Impact

Abstract Background In response to the recent serogroup W invasive meningococcal disease (IMD-W) epidemic in the Netherlands, meningococcal serogroup C (MenC) conjugate vaccination for 14-month-olds was replaced with a MenACWY conjugate vaccination, and a mass campaign targeting 14-18 year-olds was executed. We investigated the impact of MenACWY vaccination implementation in 2018-2020 on incidence rates and estimated vaccine effectiveness (VE). Methods We extracted all IMD cases diagnosed between July 2014 and December 2020 from the national surveillance system. We calculated age group-specific incidence rate ratios by comparing incidence rates before (July 2017-March 2018) and after (July 2019-March 2020) MenACWY vaccination implementation. We estimated VE in vaccine-eligible cases using the screening method. Results Overall, IMD-W incidence rate lowered by 61% (95%CI 40-74). It declined by 82% (95%CI 18-96) in vaccine-eligible age group (15-36 month-olds and 14-18 year-olds) and by 57% (95%CI 34-72) in vaccine non-eligible age groups. VE was 92% (95%CI -20-99.5) against IMD-W vaccine-eligible toddlers. No IMD-W cases were reported in vaccine-eligible teenagers after the campaign. Conclusions The MenACWY vaccination programme was effective in preventing IMD-W in the target population. The IMD-W incidence reduction in vaccine non-eligible age groups may be caused by indirect effects of the vaccination programme. However, disentangling natural fluctuation from vaccine-effect was not possible. Our findings encourage the use of toddler- and teenager MenACWY vaccination in national immunization programmes especially when implemented together with a teenager mass campaign during an epidemic.

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