Survivors Of Acute Leukemia Research Articles

小児急性骨髄性白血病（AML）経験者の就学・就労促進に関わる要因と支援

小児急性骨髄性白血病（AML）経験者の就学・就労促進に関わる要因と支援

Burden of Long-Term Morbidity Borne by Survivors of Acute Myeloid Leukemia (AML) Treated with Blood or Marrow Transplantation (BMT) – Results of the BMT Survivor Study (BMTSS)

Background: Blood or marrow transplantation (BMT) is an integral part of consolidation and/or salvage therapy for patients with acute myeloid leukemia (AML). With the growing population of AML survivors, there is a need to understand the quality of their survival. Methods: This multi-site study included 1,369 2y survivors who underwent BMT for AML between 1974 and 2014 at age ≥21y and 1,310 siblings. Using Common Terminology Criteria for Adverse Events, severe/life-threatening and fatal chronic health conditions were identified. Multivariable regression analysis was used to compare the risk of severe/life-threatening conditions and health status between survivors and siblings, and to identify risk factors for grades 3-5 chronic health conditions among BMT survivors. Findings: The cumulative incidence of severe/life-threatening conditions by age 70 was 74.7% in BMT survivors compared to 48.7% in siblings (p<0.001), yielding 3.8-fold higher odds of severe/life-threatening conditions (95%CI=3.1-4.6) among the BMT survivors. The most prevalent conditions included subsequent neoplasms, diabetes, cataracts, venous thromboembolism, and joint replacement. Survivors were more likely to report poor general health (OR=3.8, 95%CI=2.8-5.1), activity limitation (OR=3.7, 95%CI=3.0-4.5), and functional impairment (OR=2.9, 95%CI=2.3-3.6). Among BMT recipients, the 20y cumulative incidence of severe/life-threatening/fatal conditions was 68%. History of chronic graft versus host disease was associated with a higher risk of pulmonary disease (HR=3.1, 95%CI=1.0-9.3), cataract (HR=2.6, 95%CI=1.3-3.8), and venous thromboembolism (HR=2.3, 95%CI=1.2-4.6). Relapse-related mortality plateaued at 30%, while non-relapse-related mortality continued to increase, approaching 50% at 30 years. Interpretation: The burden of severe/life-threatening conditions is substantially higher in BMT recipients when compared with an unaffected comparison group, informing the need for close monitoring to anticipate and manage morbidity. Funding: This study was supported in part by grants from the National Cancer Institute (R01 CA078938, U01 CA213140), and the Leukemia Lymphoma Society (R6502-16) Declaration of Interest: None to declare. Ethical Approval: UAB serves as the single Institutional Review Board of record; participants provided informed consent

Young Survivors of Acute Myeloid Leukemia Have Long-Term Complications

Young Survivors of Acute Myeloid Leukemia Have Long-Term Complications

Survival Rate of Patients with Acute Leukemia: A Case Study in Iran

Background: Acute leukemia is a kind of aggressive disease that includes high rates of fatalities in the world, in particular in Iran. This research was done to determine the survival rate of patients with acute leukemia in Iran. Methods: 85 adult patients who were first diagnosed with acute leukemia in Shahid Bahonar hospital of Kerman during March 2012 until March 2013 were evaluated in a retrospective descriptive study to measure the death/life status in a 5-year period (2012-2017). The required data was gathered from medical records of patients, HIS system data, and the cancer registry system, and the Kaplan-Meier estimator and Log Rank test were used to calculate the survival rate using SPSS23. Results: Survival rate was completely 45.9 % for patients with acute adult leukemia. It was 47.08 % in acute myelogenous leukemia (AML) and it was 43.06 % in acute lymphocytic leukemia (ALL). The 1,2,3,4 and 5-year survival of acute leukemia was respectively 87.1 %, 69.4 %, 62.4 %, 56.5 % and 45.9 %. Conclusion: Iran's health system should design and plan to increase the survival of patients with acute leukemia by improving the methods and facilities to diagnose and treat it more quickly and more effectively.

Treatment Decision-Making and Decisional Support Experiences Among Acute Myeloid Leukemia Survivors

Background: With the availability of newer acute myeloid leukemia (AML) treatment combinations and targeted therapies, it is important for patients to understand all available treatment options, including their associated benefits, risks and side effects, before treatment decisions are made. Open communication between patients and clinicians about such options is a critical step toward collaborative treatment decision-making. The purpose of this study is to characterize AML patient experiences regarding treatment decision-making (TDM) and satisfaction with health care team (HCT) communication. Methods: Fifty-six (56) AML patients and survivors enrolled in the Cancer Support Community's online survey, the Cancer Experience Registry®. Forty (40) participants completed survey items pertinent to TDM and satisfaction with HCT communication. Items assessed participants' knowledge about treatment options prior to making a treatment decision, involvement in the TDM process, perceived preparation to discuss treatment options with their doctor, satisfaction with their doctor's explanation of the benefits of each treatment option, satisfaction with their doctor's explanation of the risks and side effects of each treatment option (response options for these five items: 0-4, where 0=Not at all and 4=Very much), and desire for additional support prior to making a treatment decision (response options: Yes/No). Frequencies for these items and socio-demographic and clinical history measures were examined. Results: Among the 40 participants who completed TDM measures, 55% were female and 95% were White, with a mean (SD) age of 52.7 (12.9) years (range: 20-77). Mean time since diagnosis was 5.6 years. Forty-three (43%) percent of participants reported that they were receiving treatment at the time of survey completion, and 28% indicated having ever experienced a recurrence of their cancer. While 65% of participants reported that they were quite a bit or very much involved in their TDM process, only 43% indicated that they were quite a bit or very much knowledgeable about their treatment options prior to making their treatment decision, and 40% of participants reported that they would have liked more support prior to making their treatment decision. More than half of respondents indicated that they were quite a bit or very much satisfied with their doctor's explanation of the benefits of each treatment option (55%), and the risks and side effects of each treatment option (58%); however, only 38% of participants indicated that they felt quite a bit or very much prepared to discuss treatment options with their doctor. Conclusions: Findings demonstrate that substantial proportions of AML patients and survivors express considerable involvement in their treatment decision-making process, and satisfaction with their doctor's explanation of the benefits and the risks and side effects of each treatment option. However, fewer individuals diagnosed with AML reported high levels of knowledge about their treatment options prior to making their treatment decision, and relatively few felt prepared to discuss treatment options with their doctor. Furthermore, many AML patients and survivors indicated a desire for additional support prior to making a treatment decision. Together, results highlight a need for resources, such as TDM guides or in-person counseling, to enhance HCT communication surrounding TDM for individuals with AML. Such efforts may provide AML patients with sufficient knowledge about treatment options to ensure that they feel adequately prepared to discuss these options and select the appropriate treatment pathway. Disclosures Kranzler: Astellas Pharma US, Inc.: Research Funding; Pharmacyclics, Inc.: Research Funding; Janssen Oncology: Research Funding; Takeda Oncology: Research Funding; Jazz Pharmaceuticals: Research Funding. Fortune:Genentech: Research Funding; Boston Scientific Foundation: Research Funding. Leblanc:UpToDate: Patents &amp; Royalties: Royalties; Agios, AbbVie, and Bristol Myers Squibb/Celgene: Speakers Bureau; AstraZeneca: Research Funding; AbbVie, Agios, Amgen, AstraZeneca, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Helsinn, Heron, Otsuka, Medtronic, Pfizer, Seattle Genetics, Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; American Cancer Society, BMS, Duke University, NINR/NIH, Jazz Pharmaceuticals, Seattle Genetics: Research Funding. Liesveld:Abbvie: Honoraria; Onconova: Other: data safety monitoring board. Zaleta:Pfizer, Inc.: Research Funding; Athenex Oncology: Research Funding; Gilead Sciences, Inc: Research Funding.

Frailty in long‐term Dutch adult survivors of childhood acute myeloid leukaemia, neuroblastoma, and Wilms' tumour

AbstractBackgroundSeveral simultaneous impairments in physical ability may be an indication of frailty in adult survivors of childhood cancer (CCS). The aim of our study was to assess the occurrence of frailty and to explore potential determinants in a selected Dutch cohort of long‐term adult CCS.MethodsIn this cross‐sectional study, we used data of 70 very long‐term CCS [median age 28.8 years (interquartile range: 23.9–34.6)] of acute myeloid leukaemia (AML) (n = 17), neuroblastoma (NBL) (n = 25), and Wilms' tumour (WT) (n = 28). Prefrailty and frailty were defined as having, respectively, 2 and ≥3 of the five following components: low relative lean body mass (by dual‐energy X‐ray absorptiometry less than −1.5 standard deviation, SD), self‐reported exhaustion (fatigue, exhaustion, or exertion related complaints), low energy expenditure (men: &lt;383 kcal/week, and women: &lt;270 kcal/week), slow walking speed (less than −2.0 SD on the 6‐min walk test), and weakness (hand grip strength less than −2.0 SD). Potential determinants of prefrailty and frailty (≥2 components), including treatment components, sociodemographic, and lifestyle factors, were evaluated using logistic regression analysis.ResultsRespectively, 6.3% and 28.1% women and 5.3% and 26.3% men were classified as frail and prefrail. Six per cent of the AML, 8% of the NBL, and 3.6% of the WT CCS were frail. Forty‐one per cent of the AML, 28% of the NBL, and 17.9% of the WT CCS were prefrail. No significant associations were found between any of the investigated determinants and frailty or prefrailty.ConclusionOur results confirm previous reports that CCS, in particular intensively treated, have a potential risk of (pre)frailty.

Changes in the hepatitis B surface antibody in childhood acute lymphocytic leukaemia survivors after treatment with the CCLG-ALL 2008 protocol.

Antibody levels after hepatitis B virus (HBV) vaccination may be affected by suppression of the immune system due to cancer therapy. As such, childhood acute lymphocytic leukaemia (ALL) survivors are at risk of HBV infection due to immunosuppression secondary to chemotherapy. However, the hepatitis B surface antibody (HBsAb)-seropositive rate of childhood ALL survivors after chemotherapy is unknown, and the need to revaccinate HBsAb-seronegative ALL survivors is not appreciated in China. To assess the changes in HBsAb before and after chemotherapy, we retrospectively analyzed clinical data from 547 patients treated with the Chinese Children Leukaemia Group (CCLG)-ALL 2008 protocol from 1April 2008 to 30August 2019. The results revealed that 416 patients (76·1%) were HBsAb-seropositive at diagnosis, and at the time of the cessation of chemotherapy, 177 patients (32·4%) were HBsAb-seropositive and 370 patients (67·6%) were HBsAb-seronegative. Interestingly, 11 patients who were HBsAb-seronegative at diagnosis converted to seropositive at the time of the cessation of chemotherapy. HBsAb titres were decreased after chemotherapy (P<0·0001). Further, patients with higher HBsAb titres at diagnosis were more likely to maintain protective antibody titres at the completion of chemotherapy (P<0·0001). The loss of antibody was more remarkable in younger patients (≤10 years) both at diagnosis (P=0·009) and at the completion of chemotherapy (P=0·006). In summary, this study showed that 67·6% of patients were HBsAb-seronegative at the time of the cessation of chemotherapy, which indicates that ALL survivors are at high risk of HBV. As a result, HBV revaccination after chemotherapy should be highly valued in ALL survivors.

Adipokines in young survivors of childhood acute lymphocytic leukemia revisited: beyond fat mass.

PurposeThis cross-sectional study evaluated the relationship between adipokines (leptin, adiponectin, visfatin, and resistin) and adiposity indexes regarding sex and cranial radiotherapy exposure among young acute lymphocytic leukemia survivors.MethodsA multivariate analysis of covariance (MANCOVA) was used to evaluate the joint effect of sex, cranial radiotherapy, and body mass index (BMI) z-score (model 1) or fat mass index (FMI) (model 2) on adipokines.ResultsThis study included 55 survivors of childhood acute lymphocytic leukemia between 15 and 23 years of age from both sexes (56.4% female); 43.6% of the sample had undergone cranial radiotherapy (18–24 Gy). The BMI z-score, the FMI, and sex (P<0.050 for all) influenced at least one adipokine, while cranial radiotherapy exposure was marginal in model 2. Parameter estimates from the MANCOVA's final model showed that the BMI z-score (β=-0.437, P=0.010) and the FMI (β=-0.209, P=0.004) negatively influenced adiponectin, while the FMI positively affected resistin (β=0.142, P=0.020). The relationship between leptin, visfatin, and the adiposity ndexes could not be established. In model 1, females presented with increased adiponectin (β=-1.014, P=0.011) and resistin (β=-1.067, P=0.002) levels; in model 2, female sex positively affected adiponectin (β=-1.515, P=0.001) and marginally influenced resistin (β=-0.707, P=0.054) levels. Cranial radiotherapy negatively determined visfatin levels in both final models (P<0.050).ConclusionsChanges in body fat may be associated with adipose tissue dysfunction and should be carefully evaluated in survivors of acute lymphocytic leukemia, considering both sex and cranial radiotherapy exposure, to treat disorders that may possibly aggravate their risk for early cardiovascular disease.

The challenge of long-term follow-up of survivors of childhood acute leukemia after hematopoietic stem cell transplantation in resource-limited countries: A single-center report from Brazil.

With the number of long-term HSCT survivors steadily increasing, attention needs to be focused on the late complications and quality of life. We therefore analyzed the outcome of 101 pediatric patients (<18years old at the time of HSCT) transplanted for acute leukemia between 1981 and 2015 at Complexo Hospital de Clínicas, Federal University of Paraná, Brazil, and who survived at least two years after HSCT. The median follow-up was 5.9years (2.0-29.0); median age at follow-up was 17.5years (2.98-39.0). The 5-year cumulative incidence of relapse was 27.5% (95% CI 18.6%-36.4%). Two-year cumulative incidence of chronic GVHD was 21.8% (95% CI 13.7%-29.8%). Of the 101 patients, 72 patients (71.3%) presented with late effects. Those surviving longer after HSCT experienced more complications. Patients who received TBI-based regimen developed more late effects (P=.013) and more endocrinological complications (P=.024). Endocrinological complications were the most common late sequelae found in this study. For childhood survivors, quality of life was not influenced by age (at HSCT or at last visit), time from HSCT, gender, donor, or GVHD. For survivors that no longer were children, only age at last visit impacted financial domain measures, irrespective of gender, donor, or GVHD. The current study confirms the high burden late complications after pediatric HSCT have on the survivors and underlines the importance of extended follow-up.

Childhood Leukemia Survivors and Metabolic Response to Exercise: A Pilot Controlled Study.

Background: Leukemia is the most common cancer in pediatrics, with many late effects such as higher risk of dyslipidemia, insulin resistance, obesity, and metabolic syndrome. The objective of this work was to investigate substrate oxidation during submaximal exercise in survivors of childhood acute leukemia. Methods: A total of 20 leukemia survivors and 20 healthy children were matched by sex, age, and Tanner stage. They all took a submaximal incremental exercise test to determine fat and carbohydrate oxidation rates. Results: Cardiorespiratory fitness was significantly lower in leukemia survivors, with lower relative VO2 peaks (p < 0.001), lower heart rate values (p = 0.02), and lower exercise power (p = 0.012), whereas rest metabolism and body mass index did not differ between the two groups. During exercise, upward of heart rate relative to VO2 peak was significantly higher (p < 0.001) in childhood leukemia survivors. We found lower carbohydrate and fat oxidation rates (p = 0.07) in leukemia survivors compared with healthy children, and also a significantly lower relative maximal fat oxidation rate (p = 0.014). Conclusion: Despite impaired physical fitness and metabolic response to exercise, childhood leukemia survivors remained sensitive to physical activity interventions, and could readily adapt to submaximal exercise intensity.

ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia

Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naïve cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize the risk of GvHD and provide graft-versus-infection and -leukemia activity. Safety and efficacy of ATIR101 administered after T-cell-depleted haploidentical HSCT (TCD-haplo + ATIR101) without posttransplant immunosuppressors were evaluated in a Phase 2, multicenter study of 23 patients with acute leukemia and compared with an observational cohort undergoing TCD-haplo alone (n = 35), matched unrelated donor (MUD; n = 64), mismatched unrelated donor (MMUD; n = 37), and umbilical cord blood (UCB; n = 22) HSCT. The primary endpoint, 6-month non-relapse mortality (NRM), was 13% with TCD-haplo + ATIR101. One year post HSCT, TCD-haplo + ATIR101 resulted in lower NRM versus TCD-haplo alone (P = 0.008). GvHD-free, relapse-free survival (GRFS) was higher with TCD-haplo + ATIR101 versus MMUD and UCB (both P < 0.03; 1-year rates: 56.5%, 27.0%, and 22.7%, respectively) and was not statistically different from MUD (1 year: 40.6%). ATIR101 grafts with high third-party reactivity were associated with fewer clinically relevant viral infections. Results suggest that haploidentical, selective donor-cell depletion may eliminate requirements for posttransplant immunosuppressors without increasing GvHD risk, with similar GRFS to MUD. Following these results, a randomized Phase 3 trial versus posttransplant cyclophosphamide had been initiated.

A Multi-Omic Precision Medicine Clinical Trial in Acute Leukemia

A Multi-Omic Precision Medicine Clinical Trial in Acute Leukemia

Chronic Health Conditions and Late Mortality Among Survivors of Childhood Acute Myeloid Leukemia: A Report from the Childhood Cancer Survivor Study (CCSS)

Introduction: Five-year survival following childhood acute myeloid leukemia (AML) has doubled over the last 4 decades due to advances in treatment and supportive care, including more widespread use of hematopoietic cell transplantation (HCT). The impact on long-term morbidity and mortality among survivors is unknown. Methods: Cumulative incidence and 95% confidence intervals (CI) for overall and cause-specific late (&amp;gt;5 years from diagnosis) mortality and CTCAE grades 3-5 chronic health conditions (CHC) were estimated among 5-year survivors of AML diagnosed &amp;lt;21 years of age between1970-99 in the CCSS. Comparisons were made by decade of diagnosis (1970s, 1980s, 1990s) and treatment (HCT vs. chemotherapy only [chemo-only]). Cox regression models estimated hazard ratios (HR) for health-related deaths and CHC based on treatment decade and HCT status. Results: Among 927 AML survivors (median age at diagnosis 7.1 years [range 1-21 years]; median age at last follow-up 29.4 years [range 8-60 years]; 16,069 person-years of follow-up; 37% treated with HCT [15% of 1970s survivors, 36% of 1980s survivors, 44% of 1990s survivors), the 20-year cumulative incidence of all-cause mortality was 6.7% (CI 4.2-9.2%) for chemo-only survivors and 13.5% (CI 9.2-17.8%) for HCT survivors. For chemo-only survivors, the highest incidence of health-related mortality were attributable to cardiac causes (1.5%, CI 0.5-2.6), relapse (0.9%, CI 0.1-1.8), and SMN (0.6%, CI 0.0-1.2), whereas for HCT survivors the highest health-related causes of death were relapse (6.5%, CI 3.7-9.2%), SMN (1.3%, CI 0-2.5%), and pulmonary causes (0.6%, CI 0-1.5%). When treatment groups were considered in multivariable Cox models, risk for late mortality was similar for chemo-only survivors from the 1990s compared to the 1970s (HR 0.4, CI 0.1-1.4), but risk was reduced for HCT survivors from the 1990s compared to the 1970s (HR 0.2, CI 0.1-0.4). The 20-year cumulative incidence of grade 3-5 CHCs among chemo-only survivors was 26.9% (CI 23.0-30.7%) compared to 46.8% (CI 40.9-52.7%) among HCT survivors, with the highest incidence occurring for cardiovascular CHC (chemo-only, 9.7%, CI 7.1-12.2%; HCT, 10.6%, CI 7.0-14.2%), pulmonary CHC (chemo-only, 1.0%, CI 0.1-1.9%; HCT, 2.9%, CI 1.0-4.8%) and SMN (chemo-only, 0.8%, CI 0.0-1.7%; HCT, 5.7%, CI 2.9-8.6%). Incidence of overall CHC decreased in more recent decades among HCT survivors (p=0.03, Figure); however, among chemo-only survivors, CHC incidence did not significantly change by decade (p=0.12). When treatment groups were considered in adjusted models, risk for CHC was similar for those treated in the 1990s compared to the 1970s among chemo-only survivors (HR 1.5, CI 1.0-2.3) and risk estimates among HCT survivors decreased over time but did not achieve statistical significance (HR 0.6, CI 0.3-1.1). Conclusions: AML survivors treated with HCT had a reduced risk of late mortality and serious CHC in more recent treatment eras. In contrast, treatment with chemo-only was not associated with differences in mortality and serious CHC risk over time. Five-year survivors treated with chemo-only had a significantly reduced risk of health-related mortality compared with HCT survivors across all treatment eras. While treatment intensification with HCT has improved the cure rates for AML in recent decades, there remains disparity in long-term outcomes among AML survivors treated with HCT vs. chemo-only. Disclosures No relevant conflicts of interest to declare.

Burden of Long-Term Morbidity Borne By Survivors of Acute Myeloid Leukemia (AML) Treated with Blood or Marrow Transplantation (BMT) - a Report from the BMT Survivor Study (BMTSS)

Background: BMT is now an integral part of consolidation and/or salvage for patients with AML. With the growing population survivors, there is a need to understand the quality of survival. This would allow for appropriate resource allocation and implementation of risk-based screening for early detection of chronic health conditions over time. Yet, a comprehensive evaluation of the long-term burden of morbidity borne by AML patients treated with BMT remains unknown. We addressed this gap by evaluating long-term severe/life-threatening/fatal chronic health conditions (CHCs) in AML patients treated with BMT using the BMTSS. Methods: Patients were eligible if they had undergone an allogeneic or autologous BMT for AML between 1974 and 2014 at one of 3 BMT centers in the US, had survived for ≥2y after BMT, and were ≥21y of age at BMT. Of the 1,113 eligible subjects, 711 (64%) participated. BMT survivors identified a nearest-age sibling to constitute an unaffected comparison group (N=1,136). Survivors and siblings completed a 231-item BMTSS survey that included questions regarding CHC diagnosis by their healthcare provider, including age at onset of CHC. Scoring was based on Common Terminology Criteria for Adverse Events ([CTCAE] v 5.0) to determine the severity of CHCs. Using multivariable logistic regression, we determined the risk of any severe (CTCAE grade 3) or life-threatening (CTCAE grade 4) CHC in survivors compared with siblings, adjusting for age at study, sex, race/ethnicity, education, annual household income and insurance status. Information regarding therapeutic exposures (pre-BMT and transplant-related) was abstracted from medical records. Cumulative incidence of CHCs (including fatal [CTCAE grade 5] CHCs) were calculated for BMT survivors, treating relapse-related death as a competing risk. Results: Mean age at BMT was 48.6±13.8y and at survey was 58.2±11.5y. Mean interval between BMT and study participation was 9.7±6.8y; 53% were females, and 78% were non-Hispanic white; 86% received allogeneic BMT (48% from an unrelated donor). Conditioning was Fludarabine/Melphalan-based in 53% and TBI-based in 35%; stem cell source was peripheral blood (70.3%), bone marrow (19.3%), and cord (10.4%). For the siblings, the mean age at survey was 56.9+13.4y; 61% were females, and 88% were non-Hispanic white. BMT survivors vs. sibs: 53.3% of the BMT survivors and 30.4% of the sibs reported grades 3-4 CHCs, placing the survivors at a 3.0-fold higher odds of grades 3-4 CHC (95%CI, 2.4-3.7, p&amp;lt;0.0001). The odds of developing the following CHCs were significantly higher in BMT survivors when compared with siblings: subsequent malignant neoplasms (SMNs: odds ratio [OR]=10.0, 95% CI, 5.5-17.9, p&amp;lt;0.0001), diabetes (OR=5.3, 95% CI, 3.0-9.3, p&amp;lt;0.0001), venous thromboembolism (OR=3.8, 95%CI, 2.5-5.8 p&amp;lt;0.0001), cataracts (OR=3.7; 95%CI, 2.7-5.0, p&amp;lt;0.0001), and major joint replacement (OR=1.5, 95% CI, 1.1-2.1, p=0.02). Among BMT survivors: The 10- and 20y cumulative incidence of a grade 3-5 CHC was 52.0%±1.4% and 66.2%±1.6%, respectively (Figure 1). 75 survivors had developed SMNs: skin (melanoma/ squamous cell [56%]), breast (13%), colon (7%), prostate (7%), and other cancers (24%). The 10- and 20y-cumulative incidence of the most common CHCs were as follows (Figure 2): SMN (10y: 17.9%±1.7%, 20y: 32.1%±2.9%), cataract (10y: 21.5%±1.9%, 20y: 31.5%±3.0%), major joint replacement (10y: 12.5%±0.9%, 20y: 17.5%±3.4%), venous thromboembolism (10y: 8.6%±1.1%, 20y: 13.2%±2.1%), and diabetes (10y: 6.0%±1.9%, 20y: 8.0%±1.5%). Conclusion: The burden of severe/life-threatening CHCs is substantially higher in BMT survivors when compared with an unaffected comparison group. The incidence of severe/ life-threatening/ fatal chronic health condition following BMT for AML exceeds 50% at 10y, and continues to increase with time, approaching 70% at 20y post-BMT. Subsequent malignant neoplasms, diabetes, thrombo-embolic events, cataracts, and major joint replacement constitute the largest burden of morbidity. These findings suggest the need for increased awareness of the long-term burden of morbidity, to ensure close monitoring of these survivors to anticipate and manage morbidity. Disclosures Weisdorf: Incyte: Research Funding; Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy.

Cancer-Related Distress and Unmet Needs Among Acute Myeloid Leukemia Survivors

Background: Individuals with acute myeloid leukemia (AML) are at risk for significant physical and psychological burden related to their illness. While overall survival rates are improving, treatments may be associated with lengthy hospitalizations, and the risk of relapse remains substantial. This study explores cancer-related distress and concerns among AML survivors, as well as supportive care received from their healthcare team. Methods: 58 AML patients and survivors enrolled in the Cancer Support Community's online Cancer Experience Registry; 38 completed CancerSupportSource® (CSS) questions, a 25-item distress screening tool in which they rated their level of concern (0=Not at all; 4=Very seriously) about emotional well-being, symptom burden and impact, body image and healthy lifestyle, healthcare team communication, and relationships and intimacy. CSS includes validated subscales that identify individuals at risk for clinically significant depression and anxiety. Participants also completed questions about their unmet needs and desired help. Pearson's correlation coefficients were used to explore bivariate associations between socio-demographic variables and clinical history with overall distress (sum of CSS ratings) in AML respondents. Results: Mean (SD) age was 50 (14) years (range: 18-77); mean time since diagnosis was 5.6 years. Participants were 87% White and 64% female. 33% were receiving treatment at the time of taking the survey; 23% had ever experienced a recurrence of their cancer. Participants' greatest concerns (% rated Moderately to Very seriously) included: eating and nutrition (61%); exercising (57%); fatigue (53%); worry about the future and what lies ahead (51%); feeling irritable (51%); health insurance or money worries (49%); sleep problems (47%); changes or disruptions in work, school, or home life (46%); and feeling sad or depressed (45%). Based on responses to CSS risk screening subscales, more than half of participants (54%) were at risk for clinically significant level of anxiety; 42% were at risk for clinically significant levels of depression. Over half of respondents indicated their healthcare team asked about emotional concerns (58%); half said they were asked about lifestyle concerns such as diet and exercise (50%) and about financial concerns (e.g., out-of-pocket costs) (50%); roughly two-out-of-five had a health professional talk to them about employment concerns (40%) or family (42%). A majority of participants wished they had received more help with managing emotions related to cancer (67%), managing short-term (50%) and long-term (61%) side effects and symptoms, changing lifestyle behaviors (53%), and financial advice/assistance (47%). In bivariate analysis, greater overall distress was associated with younger age (r=-.49; p&lt;.01), less education (r=-.44; p&lt;.01), and lower annual household income (r=-.74; p&lt;.001). Conclusions: This exploratory study demonstrates that substantial proportions of AML survivors express concerns about emotional distress, symptom burden and impact, and practical matters including finances. Yet, many report they are not counseled about these concerns, and the majority wish for more help to address these needs. Efforts are needed to enhance social and emotional support and improve access to integrated supportive care for individuals with AML, to reduce the potential impact of illness burden and distress on quality of life, treatment adherence, and other illness outcomes. Future research will examine multivariate predictors of distress and unmet needs. Disclosures Zaleta: Pfizer: Research Funding; Gilead: Research Funding; Athenex: Research Funding. Albrecht:Cancer Support Community: Membership on an entity's Board of Directors or advisory committees; Oncology Nursing Society: Honoraria; Carevive: Research Funding. LeBlanc:Medtronic: Membership on an entity's Board of Directors or advisory committees; NINR/NIH: Research Funding; Astra Zeneca: Consultancy, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; CareVive: Consultancy; Celgene: Honoraria; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Helsinn: Consultancy; Heron: Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Otsuka: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Research Funding; American Cancer Society: Research Funding; Duke University: Research Funding; Jazz Pharmaceuticals: Research Funding; Flatiron: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc: Consultancy. Liesveld:Abbvie: Membership on an entity's Board of Directors or advisory committees; Onconova: Other: Data safety monitoring board. Rogers:Teva: Speakers Bureau; Takeda: Honoraria; Genentech: Speakers Bureau; Seattle Genetics: Speakers Bureau; Abbvie: Speakers Bureau; Cardinal Health: Honoraria; Genentech: Honoraria; Mylan: Honoraria; Coherus: Speakers Bureau.

The impact of response kinetics for multiple myeloma in the era of novel agents

AbstractRapid remission by induction therapy has long been recognized as an important predictor for long-time survival in acute leukemia. However, the impact of response kinetics on multiple myeloma (MM) seems to be different and remains unexplored. The relationship between response kinetics and outcome were assessed in 626 patients with newly diagnosed MM who were included in a prospective, nonrandomized clinical trial (BDH 2008/02). Patients were assigned to either immunomodulatory drug- or proteasome inhibitor–based therapy. The response depth, time to best response (TBR) and duration of best response (DBR) were collected. Depth of response was associated with superior outcomes, consistent with findings from other studies. However, the early responders (defined as TBR ≤3 months) showed significantly worse survival compared with late responders. We found that patients with rapid complete remission experienced inferior survivals comparable to those attaining a gradual partial remission. Moreover, 4 distinct response kinetics patterns were identified. Patients with gradual and sustained remission (“U-valley” pattern) experienced superior outcomes, whereas poor outcomes were observed in rapid and transient responders (“roller coaster” pattern) (median overall survival, 126 vs 30 months). The effects of response patterns on survival were confirmed in patients at different stages of disease and cytogenetic risk, including transplant-eligible patients and those attaining different extents of response depth. Collectively, our data indicated that slow and gradual response is a favorable prognostic factor in MM. In addition to response depth, the kinetic pattern of response is a simple and powerful predictor for survival even in the era of novel agents.

Current Advances in Immunotherapy for Acute Leukemia: An Overview of Antibody, Chimeric Antigen Receptor, Immune Checkpoint, and Natural Killer

Recently, due to the application of hematopoietic stem cell transplantation and small molecule inhibitor, the survival of acute leukemia is prolonged. However, the 5 year survival rate remains low due to a high incidence of relapse. Immunotherapy is expected to improve the prognosis of patients with relapsed or refractory hematological malignancies because it does not rely on the cytotoxic mechanisms of conventional therapy. In this paper, the advances of immunotherapy in acute leukemia are reviewed from the aspects of Antibody including Unconjugated antibodies, Antibody-drug conjugate and Bispecific antibody, Chimeric Antigen Receptor (CARs), Immune checkpoint, Natural killer cells. The immunological features, mechanisms and limitation in clinic will be described.

PF593 THE IMPACT OF RESPONSE KINETICS FOLLOWING INITIAL THERAPY FOR MULTIPLE MYELOMA IN THE ERA OF NOVEL AGENTS

Background:Rapid remission has long been recognized as an important predictor for long‐time survival in acute leukemia (AL). However, the effects of response kinetics on survival seems to be different from those in AL. A rapid reduction of tumor burden probably indicates a chemotherapy‐sensitive population. But on the other hand, a high proliferative activity of plasma cell may be responsible for the rapid response. The effects of response kinetics on outcome for MM remain largely unexplored.Aims:In the era of novel drugs, the proportion of patients attaining complete remission (CR) has been significant increased. However, a deep response has not always translated into an improved survival. In both transplant‐eligible and ineligible patients, we identified different response kinetic patterns after induction therapy which are associated with distinct patient outcomes.Methods:The relationship between response kinetics and outcome were prospectively assessed in 626 patients with newly diagnosed MM that were included in a prospective, non‐randomized clinical trial (BDH 2008/02). Patients were assigned to either immunomodulatory drugs‐based or proteasome inhibitors‐based therapy. The response depth, time to best response (TBR) and duration of best response (DBR) were collected. Modified progression‐free survival (mPFS) and overall survival (mOS) from time of first detectable best response were calculated.Results:Depth of response was associated with superior outcomes, consistent with findings from other studies. However, the early responders (defined as TBR ≤ 3 months) showed significantly worse survival compared with late responders. There was no significant difference in survival between patients with a rapid CR and those with a late partial remission (PR) (mPFS 33.4 vs. 36.2 months, P = 0.382; mOS 62.6 vs. 64.2 months, P = 0.169). TBR remained an independent predictor of outcome in multivariate analysis (HR = 1.9 and HR = 2.8 for mPFS and mOS).Moreover, four distinct response kinetic patterns were identified: 1) late response and late relapse (“U‐valley” pattern) (n = 157, 25%); 2) early response and late relapse (n = 101, 16%); 3) late response and early relapse (n = 130, 21%); 4) early response and early relapse (“Roller coaster” pattern) (n = 172, 25%), and best response less than PR (n = 66, 11%). Response kinetics based stratification resulted in remarkable differences in outcome. Patients with gradual and sustained remission identified as “U‐valley” pattern experienced superior outcomes, followed by patients with “early response and late relapse” and “late response and early relapse”, while poorest outcomes were observed in rapid and transient responders (“Roller coaster” pattern) (median OS 126, 81, 44 and 30 months, respectively). The effects of response patterns on survival were confirmed in patients at different stages of disease and cytogenetic risk, including transplant‐eligible patients and those attaining different extents of response depth.Summary/Conclusion:Our data indicate that a slow and gradual response is a good prognostic factor for survival, arguing against premature change to more intensive regimens, especially for elderly or unfit patients. In addition to response depth, the kinetic pattern of response is a simple and powerful predictor for survival even in the era of novel agents.image

Fatigue in long-term survivors of acute promyelocytic leukemia (APL) and its association with other symptoms and functional limitations.

e23073 Background: Despite cancer survivorship research for patients with solid tumours is increasing, there is paucity of data for patients with hematologic malignancies. We aimed to: 1) investigate factors associated with development of fatigue in long-term APL survivors; 2) describe prevalence of other key symptoms and functional limitations by fatigue severity. Methods: The current analysis is based on 244 APL survivors with a median follow-up from diagnosis of 14.3 years, who were recruited in a large multicenter study. Fatigue was evaluated with the validated FACIT-Fatigue scale. Multivariate linear regression analysis was used to investigate factors associated with self-reported fatigue and key clinical and treatment-related variables were also considered in the analysis. Patients were also divided into two groups based on the FACIT-Fatigue median score identifying a low fatigue (LF) and a high fatigue (HF) group. Prevalence (i.e., not present, mild and moderate to severe) of key symptoms and functional limitations, measured with the EORTC QLQ-C30, were also analyzed by fatigue severity. Results: Multivariate analysis showed that a lower age at diagnosis (p = .002), absence of comorbidities (p = .001) and a greater social support (p = .004) were independently associated with lower fatigue. Patients in the HF group had a significantly higher prevalence of many symptoms, including: pain (p &lt; .001), dyspnea (p &lt; .001), insomnia (p &lt; .001), appetite loss (p = .010), nausea and vomiting (p = .026) and diarrhea (p = .002) than patients in the LF group. As an example, whilst in the HF group there were 61% of patients also reporting pain (with any level of concern), in the LF group there were only 26% of patients reporting pain. Also, HF patients reported a significantly higher prevalence of functional limitations including: physical, role, social, emotional and cognitive functioning (each with p &lt; .001). Conclusions: Our data provides novel information of factors that are independently associated with fatigue severity in long-term APL survivors. Greater fatigue is also associated with a substantial burden of other symptoms and functional limitations.

Lipodystrophy-like features after total body irradiation among survivors of childhood acute leukemia.

Background/objectiveThe number of long-term survivors of childhood acute leukemia (AL) is substantially growing. These patients are at high risk for metabolic syndrome (MS), especially those who received total body irradiation (TBI). The consequences of children’s irradiation on adipose tissue (AT) development in adulthood are currently unknown. The objective of this study is to assess the impact of TBI on AT of childhood AL survivors.DesignWe compared the morphological and functional characteristics of AT among survivors of childhood AL who developed MS and received (n = 12) or not received (n = 12) TBI.Subjects/methodsBody fat distribution and ectopic fat stores (abdominal visceral and liver fat) were evaluated by DEXA, MRI and 1H-spectroscopy. Functional characteristics of subcutaneous AT were investigated by studying gene expression and pre-adipocyte differentiation in culture.ResultsPatients who have received TBI exhibited a lower BMI (minus 5 kg/m2) and a lower waist circumference (minus 14 cm), especially irradiated women. Despite the lower quantity of intra-abdominal AT, irradiated patient displayed a nearly two-fold greater content of liver fat when compared to non-irradiated patient (17 vs 9%, P = 0.008). These lipodystrophic-like features are supplemented by molecular abnormalities in subcutaneous AT of irradiated patients: decrease of gene expression of SREBP1 (minus 39%, P = 0.01) and CIDEA (minus 36%, P = 0.004) and a clear alteration of pre-adipocyte differentiation.ConclusionsThese results strongly support the direct effect of irradiation on AT, especially in women, leading to specific nonalcoholic fatty liver disease, despite lower BMI. A long-term appropriate follow-up is necessary for these patients.