Hematopoietic Cell Transplantation Cohort Research Articles

Economic Burden of Hematopoietic Cell Transplantation (HCT) Among Commercially Insured Patients with Hematological Malignancies in the United States (US)

INTRODUCTION: HCT is a potentially curative treatment option for high-risk hematologic malignancies. Approximately 20,000 HCTs are performed in the US annually. A wide range of costs for both autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT) are reported. For commercially insured patients with hematologic malignancies, the economic burden of an auto-HCT was estimated at $390,159 and allo-HCT at $745,341 in 2011-2014 over a 6-month pre- and 12-month post-HCT period (Bonafede 2017), indirect and caregiver costs may further increase burden (Applebaum 2017; Denzen 2017). We characterize all-cause healthcare resource utilization (HRU) and costs among commercially insured patients with hematologic malignancies who received an auto- or allo-HCT in a more contemporary era. METHODS: Adults with hematologic malignancies and ≥1 inpatient admission for an auto- or allo-HCT (Jan 2015-Mar 2020) were identified from the MarketScan Commercial and Medicare Supplemental Databases. Patients were indexed on the date of first HCT inpatient admission. Included patients had 12 months of continuous enrollment before and after the index date and ≥2 medical claims with a diagnosis code for an eligible hematologic malignancy (acute myeloid leukemia, myelodysplastic syndrome, myelofibrosis, myeloproliferative disease, acute lymphoblastic leukemia, chronic myeloid leukemia, multiple myeloma, Hodgkin disease, or lymphoma) with ≥1 claim occurring on or before the index date. Patients with an HCT prior to the index date were excluded. Controls were selected from patients meeting study criteria with the exception of an HCT claim requirement. The index date for patients in the control group was randomly assigned based on the time between diagnosis and HCT for the HCT cohorts. Controls and HCT recipients were matched 3:1 based on age, sex, insurance type, Deyo-Charlson Comorbidity Index categories, and hematologic malignancy. Total all-cause HRU and inpatient, outpatient (ie, ED [emergency department], physician office, other visits), and pharmacy costs were compared between the HCT cohorts and controls over the 6-month pre- and 12-month post-index periods. Healthcare costs (2021 US$) were based on paid amounts of adjudicated claims, including insurer/health plan payments and patient cost-sharing (copayment, deductible, and coinsurance). RESULTS: A total of 1653 auto-HCT recipients were matched to 4959 controls and 411 allo-HCT recipients matched to 1233 controls. After matching, HCT cohorts and controls were similar in age, sex, insurance type (Table 1), Deyo-Charlson Comorbidity Index categories, and hematologic malignancy. Pre-index comorbidities differed among the HCT and control cohorts, with psychiatric disturbances, infections, and heart valve disease significantly more common in both the auto- and allo-HCT recipients vs matched controls (P<0.001 for all). Multiple myeloma was the most common eligible indication for auto-HCT whereas acute myeloid leukemia/myelodysplastic syndrome/myelofibrosis/myeloproliferative disease were the most common indications for allo-HCT. Over the 18-month observation period, total all-cause costs were significantly higher for auto-HCT recipients vs matched controls ($540,194 vs $182,846; P<0.001; Figure 1), with auto-HCT recipients having significantly higher costs than controls for all categories evaluated except ED visits during the post-index period ($817 vs $879; P<0.4). Auto-HCT costs were driven by inpatient and outpatient costs. For allo-HCT recipients vs matched controls, total all-cause costs were significantly higher ($929,799 vs $190,776; P<0.001) during the 18-month observation period, with allo-HCT recipients having significantly higher costs than controls for all categories evaluated except ED visits during the pre- and post-index periods ($568 vs $533; P=0.11, $824 vs $862; P>0.9). Inpatient costs were the primary cost driver for allo-HCT recipients. CONCLUSIONS: The use of HCT, a potentially curative treatment for some patients with hematologic malignancies, is associated with considerable HRU and economic burden. This analysis did not include indirect costs, caregiver burden, or donor costs, and therefore likely underestimates the true burden of HCT for patients with hematologic malignancies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparing Survival Outcomes of Autologous and Allogeneic Hematopoietic Cell Transplantation in Patients with Relapsed/Refractory Nodal Peripheral T-Cell Lymphoma

Background Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphoma and carries a poor prognosis. The four most common types are PTCL-NOS, angioimmunoblastic T cell lymphoma (AITL), and anaplastic large T cell lymphoma (ALCL) with or without ALK and together are grouped as nodal PTCL. In relapsed/refractory disease (r/r), the survival outcomes are poor and estimated to be approximately 13.7 months (Mak, Hamm et al. 2013). Hematopoietic cell transplantation (HCT) has been used to consolidate response and improve outcomes. However, the role of autologous HCT (auto HCT) and allogeneic HCT (allo HCT) remains controversial. Here we aim to compare the survival outcomes of auto HCT and allo HSCT in r/r PTCL. Methods We retrospectively reviewed clinical data on 53 patients at Moffitt Cancer Center who developed r/r nodal PTCL and received HCT from 12/2007 to 12/2021. Patients who had auto HCT during the first remission were excluded. Physician discretion, donor availability, among others, were the factors that influenced transplant type allocation. Clinical data were abstracted in accordance with institutional review board-approved protocol. Patients were divided into two subgroups: cohort A) auto HCT and cohort B) allo HCT. The baseline clinical data of two cohorts were summarized using descriptive statistics and compared using Kruskal-Wallis tests for continuous variables and Chi-squared tests for categorical variables. Overall survival (OS) was calculated from the date of HCT to death or censored to the last follow-up. Median OS was calculated using the Kaplan Meier method and compared two cohorts with a log-rank test. Univariate and multivariate Cox proportional hazard (PH) using the backward elimination method were used to evaluate the association between OS and types of transplants. Results Out of 53 patients, 30 (57%) patients received auto HCT (cohort A), while 23 (43%) patients received allo HCT (cohort B). All patients achieved either partial response (PR) or complete response (CR) prior to transplant. The patients in allo cohort B were younger at the time of transplant (median age: 60 years vs. 50 years for cohort A and B, respectively, p=0.06), had a higher proportion of refractory disease (27% vs. 65% for cohort A and B, respectively, p=0.005), and had a higher proportion of PTCL-NOS (33% vs. 65% for cohort A and B, respectively, p=0.006) (table 1). ECOG status at transplant and IPI at the time of diagnosis were not significantly different between the two groups. Median OS was 40 months in cohort A compared to 57 months in cohort B, however, no statistical difference was present (p=0.49) (Figure 1). In the univariate analysis, HR for allo HCT was 0.77 (p=0.5). When adjusted for ECOG status at transplant, histology subtypes, IPI score at diagnosis in the multivariate analysis, allo HCT was associated with prolonged OS with an HR of 0.41 (p=0.045). At the study cutoff with a median follow-up of 57 months in cohort A, 18 patients died. Out of 12 patients with a known cause of death in cohort A, 7 patients (38%) died from relapse disease. With a median follow-up of 73 months in cohort B, 10 patients died. Out of 10 patients with a known cause of death, 2 patients (20%) died from the relapsed disease. Conclusion Our data showed that allo HCT in r/r PTCL is associated with improved survival compared to auto HCT in multivariate analysis. Our result supports the use of allo HCT, especially in the younger/fit population and in refractory disease. Larger studies are needed to validate our results. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Barriers to Access to Hematopoietic Cell Transplantation among Patients with Acute Myeloid Leukemia in Virginia

Allogeneic hematopoietic cell transplantation (HCT) is a standard therapy for patients with intermediate to high-risk acute myeloid leukemia (AML) and is associated with improved long-term disease-free survival. Disparity exists in access to HCT among different patient populations and requires further study.In this study, we compared HCT rates for AML among different regions in the state of Virginia and identified geographic and socioeconomic factors associated with the likelihood of receiving HCT.We conducted a retrospective, cohort study of patients 18 to 74 years of age diagnosed with AML in Virginia from 2013 to 2017 as reported to the Virginia Cancer Registry (VCR); the VCR was further linked with the Center for International Blood and Marrow Transplant Research database for identification of patients who had undergone HCT within 2 years of diagnosis. Socioeconomic data were generated from the VCR and the American Community Survey. Univariate and multivariable logistic regression models were used to examine selected socioeconomic factors of interest, including patient-level information such as sex, age, race, marital status, and primary insurance payer, as well as factors associated with geography, including the Social Vulnerability Index (SVI) and percentage of African Americans residing in the region.In Virginia, 818 patients were diagnosed with AML from 2013 to 2017, and, of these, 168 patients (21%) underwent HCT within 2 years of diagnosis. Median age was lower in the HCT cohort (55 years) versus the non-HCT cohort (64 years) (P < .001). There was a higher proportion of married patients in the HCT cohort (67%) versus the non-HCT cohort (53%) (P = .005). The rate of HCT varied by geographic region (P = .004). The multivariable analyses (without including SVI) showed decreased likelihood of HCT with increasing age (odds ratio [OR], .96; 95% confidence interval [CI], .95 to .98). Patients from regions that had a greater than 25% African American population were less likely to undergo HCT (OR, .58; 95% CI, .38 to .89). Patients who were not married were less likely to undergo HCT compared with married patients (OR, .56; 95% CI, .36 to .88). Patients with government-sponsored insurance as the primary payer were less likely to undergo HCT compared with patients with private insurance (OR, .49; 95% CI, .32 to .77). Patients living in Zip Code areas with a greater percentage of population with a bachelor's or graduate degree were more likely to undergo HCT (OR, 1.02; 95% CI, 1.00 to 1.03). In a separate multivariate model with SVI, patients residing in a Zip Code with higher SVI were less likely to undergo HCT (OR, .37; 95% CI, .16 to .82).From 2013 to 2017, we found that the likelihood of a patient undergoing HCT in Virginia for AML within 2 years of diagnosis was negatively associated with increasing age, percent of African Americans residing in the region, not-married relationship status, government-sponsored insurance as primary payer, higher SVI, and decreased percent of population with a bachelor's or graduate degree. Resources should be directed toward at-risk patient populations to remove barriers to improve access to HCT. The SVI can be used to identify communities at risk nationwide.

Longitudinal Changes in Body Composition Following Hematopoietic Cell Transplantation

Sarcopenia, the loss of skeletal muscle tissue, has been identified as a potential risk factor for adverse outcomes in hematopoietic cell transplantation (HCT) recipients. However, much remains unknown about longitudinal changes in body composition following HCT. We retrospectively evaluated computed tomography (CT) imaging from 315 lymphoma patients undergoing HCT at our institution between 2000 and 2014. Two HCT cohorts were established: auto-HCT (did not receive allo-HCT, n=218) and allo-HCT (may have received previous auto-HCT, n=97). Cross-sectional area of lean muscle, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were measured at the level of the third lumbar vertebral body (L3) on an axial CT image prior to HCT, 1 year post-HCT, and 2.5 years post-HCT. Lean muscle was normalized for height and reported as L3 skeletal muscle index (L3SMI). Sarcopenia was defined as L3SMI ≤39 cm2/m2 for women and ≤55 cm2/m2for men.Sarcopenia prior to HCT was observed in 50% of HCT recipients, 47% in the auto-HCT cohort and 57% in the allo-HCT cohort. The number of lines of therapy prior to HCT was predictive of sarcopenia prior to HCT (OR=1.29, p=.01). There was a significant decline in skeletal muscle mass over time for patients in the allo-HCT cohort when compared to the trend in the auto-HCT cohort (-6.52 cm2/imaging interval, p=<0.01) (Figure 1). In the allo-HCT cohort, the association between the change in muscle mass (per cm2) from prior to HCT to 2.5 years post-HCT and moderate-severe chronic GVHD did meet statistical significance (OR 1.04, p=0.03). The incidence of sarcopenia increased over time in all patients receiving HCT (OR=1.55; p=0.02), particularly driven by patients undergoing allo-HCT who experienced an increased rate of sarcopenia over time compared to auto-HCT (OR=1.66, p=0.02). The incidence of sarcopenia reached 66% at 2.5 years post-HCT in the allo-HCT cohort (Figure 2). In the allo-HCT cohort, the association between sarcopenia at 2.5 years post-HCT and moderate-severe chronic GVHD did not meet statistical significance (OR 3.32, p=0.07). Adipose tissue analysis showed allo-HCT recipients had lower measurements of SAT at all time point when compared to patients in the auto-HCT cohort. There was a significant increase in both VAT and SAT experienced by recipients of auto-HCT and allo-HCT when comparing CT images from 1 year post-HCT and 2.5 years post-HCT (p<0.05). However, there was no significant difference in change in SAT or VAT over time when comparing auto-HCT and allo-HCT cohorts.In conclusion, retrospective analysis of CT imaging revealed significant loss of muscle mass and an increased incidence of sarcopenia following HCT, especially in patients undergoing allo-HCT. Future studies are needed to further characterize changes in body composition in HCT recipients and investigate its impact on HCT outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Home Spirometry Telemonitoring for Early Detection of Bronchiolitis Obliterans Syndrome in Patients with Chronic Graft-versus-Host Disease

Early detection of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) depends on recognition of subclinical spirometric changes, which is possible only with frequent interval spirometry. We evaluated the feasibility of home monitoring of weekly spirometry via a wireless handheld device and a web monitoring portal in a cohort of high-risk patients for the detection of lung function changes preceding BOS diagnosis. In this observational study, 46 patients with chronic graft-versus-host disease or a decline in forced expiratory volume in 1 second (FEV1) of unclear etiology after allogeneic HCT were enrolled to perform weekly home spirometry with a wireless portable spirometer for a period of 1 year. Measurements were transmitted wirelessly to a Cloud-based monitoring portal. Feasibility evaluation included adherence with study procedures and an assessment of the home spirometry measurements compared with laboratory pulmonary function tests. Thirty-six patients (78%) completed 1 year of weekly monitoring. Overall adherence with weekly home spirometry measurements was 72% (interquartile range, 47% to 90%), which did not meet the predetermined threshold of 75% for high adherence. Correlation of home FEV1 with laboratory FEV1 was high, with a bias of 0.123 L (lower limit, -0.294 L; upper limit, 0.541 L), which is within acceptable limits for reliability. Of the 12 patients who were diagnosed with BOS or suspected BOS during the study period, 9 had an antecedent FEV1 decline detected by home spirometry. Our data indicate that wireless handheld spirometry performed at home in a high-risk HCT cohort is feasible for close monitoring of pulmonary function and appears to facilitate early detection of BOS.

Geographic Disparities of Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Patients in Virginia

Introduction: Hematopoietic cell transplantation (HCT) is a standard therapy for patients with intermediate to high-risk acute myelogenous leukemia (AML), associated with improved long-term disease-free survival. Virginia is a diverse state, with rural and urban areas, including wealthy and disadvantaged counties. In this study, we compared HCT rates among different regions in the state of Virginia, and analyzed the impact of race/ethnicity, urban vs rural location, primary insurance payor, and socioeconomic status on access to HCT. Methods: We conducted a retrospective, cohort study of patients age 18-75 diagnosed with AML in Virginia from 2013-2017 as reported to the Virginia Cancer Registry (VCR); the VCR was further linked with the Center for International Blood and Marrow Transplant Research (CIBMTR) database for identification of patients who had undergone HCT within two years of diagnosis. Socioeconomic data were generated from the VCR and the American Community Survey (ACS). Univariate and multivariable logistic regression models were used to examine several socioeconomic factors of interest, including patient-level information such as sex, age, race, marital status, primary insurance payor, and distance to closest transplant center as well as factors associated with geography, including specific regions (see Figure 1) and percentage of African Americans residing in the region (see Figure 2). Results: There were 818 patients diagnosed with AML in Virginia from 2013-2017, and of these, 168 (21%) underwent HCT within two years of diagnosis. Median age was lower in the HCT cohort vs. the non-HCT cohort, 55 vs. 64 (p=&amp;lt;0.0001). There was a higher proportion of married patients in the HCT cohort vs. the non-HCT cohort, 67% vs. 53% (p=0.005). The rate of HCT varied by geographic region (p=0.004; see Figure 1). The univariate and multivariate analyses (see Table 1) showed decreased likelihood of HCT with increasing age (OR: 0.96; 95% CI: 0.95-0.98). Patients from regions which had greater than 25% African American population were 42% less likely to undergo HCT (OR: 0.58; 95% CI: 0.38-0.89) (see Figure 2). Patients who were not married were less likely to undergo HCT compared to married patients (OR 0.56; 95% CI: 0.38-0.92). Patients with government insurance as primary payor were less likely to undergo HCT compared to patients with private insurance (OR 0.49; 95% CI: 0.32-0.77). Patients living in areas (by zip code) with a greater percentage of population with a college/graduate degree were more likely to undergo transplant than the patients living in areas with a lower percentage of college/graduate degree (OR: 1.02; 95% CI: 1.00-1.03). Conclusion: From 2013-2017, only 21% of patients with AML in Virginia underwent HCT within two years of diagnosis. We found that the likelihood of undergoing HCT is associated with age, percent of African Americans residing in the region, marital status, primary insurance payor, and percent of population with a bachelor or graduate degree. Our findings suggest geographic and socioeconomic factors are likely barriers to access to HCT. The decreased rate of HCT in regions with a higher percent of African-Americans may reflect structural racism, both due to factors outside and within the medical community. Resources should be devoted to specific interventions addressing disadvantaged populations, including early human leukocyte antigen (HLA) typing, caregiving resources, increased diversity of donor pool, and improved insurance coverage. Future studies will evaluate access to HCT after referral to HCT centers as well as racial disparity in access to HCT across the United States. Disclosures Balkrishnan: Merck and Co.: Consultancy. Devine:Magenta Therapeutics: Consultancy.

Updated risk-oriented strategy for acute lymphoblastic leukemia in adult patients 18\u201365 years: NILG ALL 10/07

An updated strategy combining pediatric-based chemotherapy with risk-oriented allogeneic hematopoietic cell transplantation (HCT) was evaluated in Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph− ALL) and compared with a published control series. Following induction–consolidation chemotherapy, responsive patients were assigned to receive maintenance chemotherapy or undergo early HCT according to the risk stratification criteria and minimal residual disease (MRD) status. Of the 203 study patients (median age 41 years, range 17–67), 140/161 with Ph− ALL achieved complete remission (86.9%; 91.6% ≤55 years, P = 0.0002), with complete MRD clearing in 68/109; 55 patients were assigned to maintenance chemotherapy, and 85 to HCT due to very high-risk characteristics (hyperleukocytosis, adverse genetics, early/mature T-precursor ALL, and MRD persistence). The 5-year relapse incidence was 36%, and the treatment-related mortality rate was 18%. Median overall and relapse-free survival were 7.4 and 6.2 years, with rates of 54 and 53% at 5 years, respectively, which were significantly better than those obtained with the historical protocol (P = 0.001 and P = 0.005, respectively), without significant differences between maintenance and HCT cohorts. In prognostic analysis, MRD negativity and age ≤55 years were the most favorable independent prognostic factors. A reduction in treatment toxicity and further improvements in the risk definitions and risk-oriented design are the focuses of this ongoing research.

Survivorship in AML – a landmark analysis on the outcomes of acute myelogenous leukemia patients after maintaining complete remission for at least 3 years

Acute myeloid leukemia (AML) carries poor survival and high recurrence rate. We conducted a retrospective analysis of AML patients (N = 453) treated with chemotherapy only or chemotherapy + hematopoietic cell transplant (HCT) who maintained their first complete remission (CR) for ≥3 years. Prior comorbidities, new comorbidities, secondary malignancies, late relapse, and causes of death (COD) were documented. New comorbidities for chemotherapy only patients (n = 304) included renal disease (10%), and osteopenia/osteoporosis (38%) for HCT patients (n = 149). Incidence of hypertension was similar in the chemotherapy only cohort and chemotherapy + HCT cohort (14% vs 17%). Secondary malignancies occurred in 13%, commonly skin, prostate and breast cancers. Common COD included: secondary malignancy (4%), HCT complications (3%), and late relapses (5%). Overall, 12% had a late relapse. Median overall survival for chemotherapy only and HCT was 10.7 and 12.7 years, respectively. Long-term AML survivors need routine monitoring for comorbidities, secondary malignancies, and late relapses.

Early CD4+ T cell reconstitution as predictor of outcomes after allogeneic hematopoietic cell transplantation

Background: An association between early CD4+ T cell immune reconstitution (CD4+ IR) and survival after T-replete allogeneic hematopoietic cell transplantation (HCT) has been previously reported. Here we report validation of this relationship in a separate cohort that included recipients of ex vivo T-cell-depleted (TCD) HCT. We studied the relationship between CD4+ IR and clinical outcomes.Methods: A retrospective analysis of children/young adults receiving their first allogeneic HCT for any indication between January 2008 and December 2017 was performed. We related early CD4+ IR (defined as achieving >50 CD4+ T cells/µL on two consecutive measures within 100 days of HCT) to overall survival (OS), relapse, non-relapse mortality (NRM), event-free survival (EFS) and acute graft-versus-host disease (aGVHD). Fine and Gray competing risk models and Cox proportional hazard models were used.Results: In this analysis, 315 patients with a median age of 10.4 years (interquartile range 5.0–16.5 years) were included. The cumulative incidence of CD4+ IR at 100 days was 66.7% in the entire cohort, 54.7% in TCD (N = 208, hazard ratio [HR] 0.47, P < 0.001), 90.0% in uCB (N = 40) and 89.6% in T-replete (N = 47) HCT recipients. In multi-variate analyses, not achieving early CD4+ IR was a predictor of inferior OS (HR 2.35, 95% confidence interval [CI] 1.46–3.79, P < 0.001) and EFS (HR 1.80, 95% CI 1.20–2.69, P = 0.004) and increased NRM (HR 6.58, 95% CI 2.82–15.38, P < 0.001). No impact of CD4+ IR on relapse or aGVHD was found. Within the TCD group, similar associations were observed.Conclusion: In this HCT cohort, including recipients of TCD HCT, we confirmed that early CD4+ IR was an excellent predictor of outcomes. Finding strategies to predict or improve CD4+ IR may influence outcomes.

Outcomes of Hematopoietic Cell Transplantation in Acute Promyelocytic Leukemia – a Single Institution Experience

<h3>Background</h3> Outcomes of patients with acute promyelocytic leukemia (APL) have improved; however, a significant number of patients still relapse despite receiving all-trans-retinoic acid (ATRA) and arsenic-based therapies. We present single institution outcomes of autologous (auto) and allogenic (allo) hematopoietic cell transplantation (HCT) in patients with relapsed APL. <h3>Methods</h3> Outcomes in patients with relapsed APL who underwent either auto- or allo- HCT at Moffitt Cancer Center from 1990 to 2018 were reviewed utilizing the clinical data obtained from BMT Research & Analysis Information Network (BRAIN). Survival data were analyzed using Kaplan-Meier estimates. <h3>Results</h3> <b>Autologous HCT Cohort:</b> A total of 15 received auto-HCT with a median age at HCT of 39 (range, 21-60) years. Only 3/8 patients with known disease risk at time of diagnosis had high risk disease (high=3, low=5). Disease status at HCT were first complete remission (CR1) in 5 (33%) and CR2 in 10 (67%). All 8 patients who had minimal residual disease evaluation had negative PCR for PML-RARA. The median progression-free survival (PFS) for auto HCT was 12.9 (95% confidence interval (CI): 1.2-24.8) years. With a median follow up of 45.1 months for surviving patients, overall survival (OS) for auto HCT was 12.9 (95%CI: 0-27.8) years. <h3>Allogeneic HCT Cohort</h3> A total of 9 patients received allo HCT with a median age at HCT of 43 (range, 22-56) years. All six patients with known disease risk at time of diagnosis were either intermediate (n=2) or high risk disease (n=4). Disease status at allo HCT was CR2 in 1, CR3 in 6, and two had refractory disease. Two patients had prior auto HCT. 5/6 patients who had minimal residual disease evaluation had negative PCR for PML-RARA. Donor type was HLA-identical sibling=5; one antigen-mismatched sibling=1; HLA-matched unrelated donor=2; related haploidentical=1. Conditioning regimen intensity was myeloablative in six and reduced intensity in three of the patients. Six patients received tacrolimus-based graft-versus-host disease (GVHD) prophylaxis. The median PFS for allo HCT was 11.9 (95%CI: 0-24.1) months. With a median follow up of 48.2 months for surviving patients, OS for allo HCT was 14.2 (95%CI: 6.5-21.9) months. <h3>Conclusions</h3> In our single center analysis, auto HCT resulted in a durable remission and prolonged survival. Outcomes after allo HCT were suboptimal primarily due to their heavily pretreated condition and chemotherapy resistant disease.

Early CD4+ T Cell Reconstruction As Predictor for Outcomes after Allogeneic Hematopoietic Cell Transplantation in Pediatric and Young Adult Patients: A Validation Cohort Analyses

BackgroundAn association between early CD4+ recovery and survival after T-replete allogeneic Hematopoietic Cell Transplantation (HCT) in pediatric and young adult patients was previously reported (Admiraal et al, JACI 2017). However, validation in a separate cohort and in patients undergoing ex vivo T cell depleted (TCD) HCT is lacking. Therefore, we studied the relation between CD4+ T cell immune reconstitution (IR) and clinical outcomes, in a setting where a majority of patients received a TCD HCT.MethodsWe performed a retrospective analysis of data on children and young adults receiving their 1st allo-HCT for any indication between Jan-2008 and Dec-2017. The main goal was to relate CD4 IR (measured every 2-4 wks), within 100 days after HCT to the outcomes of interest. The main outcome of interest was overall survival (OS). Other outcomes of interest were non-relapse mortality (NRM), event-free survival (EFS), relapse and acute graft-versus-host-disease (aGvHD) grade 2-4. CD4 IR was defined according to previous studies, as having more than 50 CD4+ T cells/uL at 2 consecutive measurements within 100 days. Cox-proportional hazard and Fine and Gray competing risk models were used (R version 1.2.1335)Findings315 patients (220 Malignant, 95 non-malignant indications) were included, with a median age of 10.4 years (IQR 5.0–16.5yr). 66.0% (208/315) of the patients received a TCD graft, 12.7% (40/315) received cord blood, and 21.2% (67/315) T-replete bone marrow. The CI of CD4+ IR at 100 days was 66.7%. Incidence of achieving CD4 IR after TCD was lower compared to other cell sources, 54.7% vs 90.0% after cord blood and 89.6% after T-replete bone marrow (HR 0.47, P<0.001). The other multivariate predictors for CD4+ IR were age (continuous; 0.97, p=0.002) and mismatch MUD (HR 0.5, p=0.005). No impact of CD4+ IR on relapse or aGvHD grade 2-4 was found. Absence of CD4 IR was found to be a predictor for inferior OS (HR: 2.35, 95% CI 1.46-3.79, P<0.001; Fig 1A), and EFS (HR: 1.80, 95% CI 1.20–2.69, P=0.004) and increased NRM (HR: 6.58, 95% CI 2.82–15.38, P < 0.001; Fig 1B).InterpretationWe confirmed, in a separate HCT cohort, that early CD4 IR is a strong predictor for outcomes. Early CD4+ IR is an excellent biomarker for outcomes after HCT and should therefore be considered as a standard outcome measure. Finding strategies to better predict CD4+ T cell recovery after HCT may influence outcomes/survival in the future. An association between early CD4+ recovery and survival after T-replete allogeneic Hematopoietic Cell Transplantation (HCT) in pediatric and young adult patients was previously reported (Admiraal et al, JACI 2017). However, validation in a separate cohort and in patients undergoing ex vivo T cell depleted (TCD) HCT is lacking. Therefore, we studied the relation between CD4+ T cell immune reconstitution (IR) and clinical outcomes, in a setting where a majority of patients received a TCD HCT. We performed a retrospective analysis of data on children and young adults receiving their 1st allo-HCT for any indication between Jan-2008 and Dec-2017. The main goal was to relate CD4 IR (measured every 2-4 wks), within 100 days after HCT to the outcomes of interest. The main outcome of interest was overall survival (OS). Other outcomes of interest were non-relapse mortality (NRM), event-free survival (EFS), relapse and acute graft-versus-host-disease (aGvHD) grade 2-4. CD4 IR was defined according to previous studies, as having more than 50 CD4+ T cells/uL at 2 consecutive measurements within 100 days. Cox-proportional hazard and Fine and Gray competing risk models were used (R version 1.2.1335) 315 patients (220 Malignant, 95 non-malignant indications) were included, with a median age of 10.4 years (IQR 5.0–16.5yr). 66.0% (208/315) of the patients received a TCD graft, 12.7% (40/315) received cord blood, and 21.2% (67/315) T-replete bone marrow. The CI of CD4+ IR at 100 days was 66.7%. Incidence of achieving CD4 IR after TCD was lower compared to other cell sources, 54.7% vs 90.0% after cord blood and 89.6% after T-replete bone marrow (HR 0.47, P<0.001). The other multivariate predictors for CD4+ IR were age (continuous; 0.97, p=0.002) and mismatch MUD (HR 0.5, p=0.005). No impact of CD4+ IR on relapse or aGvHD grade 2-4 was found. Absence of CD4 IR was found to be a predictor for inferior OS (HR: 2.35, 95% CI 1.46-3.79, P<0.001; Fig 1A), and EFS (HR: 1.80, 95% CI 1.20–2.69, P=0.004) and increased NRM (HR: 6.58, 95% CI 2.82–15.38, P < 0.001; Fig 1B). We confirmed, in a separate HCT cohort, that early CD4 IR is a strong predictor for outcomes. Early CD4+ IR is an excellent biomarker for outcomes after HCT and should therefore be considered as a standard outcome measure. Finding strategies to better predict CD4+ T cell recovery after HCT may influence outcomes/survival in the future. Figure 1.Figure 1 View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Outcomes of Hematopoietic Cell Transplantation in Acute Promyelocytic Leukemia - a Single Institution Experience

BACKGROUND: Outcomes of patients with acute promyelocytic leukemia (APL) have improved; however, a number of patients, particularly those with high-risk APL, still relapse despite all-trans-retinoic acid (ATRA) and arsenic-based therapies. We present single institution outcomes of autologous (auto) and allogenic (allo) hematopoietic cell transplantation (HCT) in patients with relapsed APL. PATIENTS AND METHODS: We retrospectively reviewed outcomes in patients with relapsed APL who underwent either auto- or allo- HCT at Moffitt Cancer Center from 1990 to 2018 utilizing the clinical data obtained from BMT Research &amp; Analysis Information Network (BRAIN). Survival data were analyzed using Kaplan-Meier estimates. RESULTS: Autologous HCT Cohort: A total of 15 received auto-HCT with a median age at HCT of 39 (range, 21-60) years. Disease status at HCT were first complete remission (CR1) in 5 (33%) and CR2 in 10 (67%). Majority of patients (13/15, 87%) received busulfan/cyclophosphamide (Bu/Cy) conditioning and remaining (2/15, 13%) Bu/Cy/etoposide. All (n=15) patients received peripheral blood (PB) stem cell grafts. Median time to neutrophil engraftment was 11 (range, 10-14) days and platelet recovery was 14 (range 9-44) days. The median progression-free survival (PFS) for auto HCT was 12.9 (95% confidence interval (CI): 1.2-24.8) months. With a median follow up of 45.1 months for surviving patients, overall survival (OS) for auto HCT was 12.9 (95%CI: 0-27.8) years. At the time analysis, 8 patients were relapse-free. Allogeneic HCT Cohort: A total of 10 patients received allo HCT with a median age of 46 (range, 22-56) years at HCT. Disease status at allo HCT was CR2 in 2, CR3 in 6, and two had refractory disease. Two patients had prior auto HCT. Donor type was HLA-identical sibling=5; one antigen-mismatched sibling=1; HLA-matched unrelated donor=3; related haploidentical=1. Seven patients received peripheral blood graft and 3 received bone marrow graft. Conditioning regimen intensity was myeloablative in 7 (fludarabine/busulfan +/- anti-thymocyte globulin=3; Bu/Cy=3; cyclophosphamide/total body irradiation=1), and reduced intensity in 3 (fludarabine/melphalan=2; fludarabine/cyclophosphamide/total body irradiation=1). Seven patients received tacrolimus-based graft-versus-host disease (GVHD) prophylaxis. Median time of neutrophil engraftment was 15 (range, 12-22) days, and platelet engraftment was 22 (range, 15-28) days. The median PFS for allo HCT was 11.9 (95%CI: 2.1-21.6) months. With a median follow up of 48.2 months for surviving patients, median OS for allo HCT was 12.4 (95%CI: 4.8-19.9) months. At the time of analysis 4 patients were relapse-free. CONCLUSIONS: In our single center analysis, auto HCT for APL resulted in a durable remission and prolonged survival. Outcomes after allo HCT were suboptimal primarily due to their heavily pretreated condition and chemotherapy resistant disease. Further research on novel conditioning regimen and relapse prevention is needed to improve the outcomes of allo HCT in APL. Figure Disclosures Lancet: Jazz Pharmaceuticals: Consultancy; Agios Pharmaceuticals: Consultancy; Daiichi-Sankyo: Consultancy; Pfizer: Consultancy. Sweet:Pfizer: Consultancy; Celgene: Speakers Bureau; Jazz: Speakers Bureau; Incyte: Research Funding; Stemline: Consultancy; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Komrokji:JAZZ: Speakers Bureau; Novartis: Speakers Bureau; Agios: Consultancy; JAZZ: Consultancy; Incyte: Consultancy; pfizer: Consultancy; DSI: Consultancy; celgene: Consultancy. Bejanyan:Kiadis Pharma: Other: advisory board. List:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nishihori:Novartis: Research Funding; Karyopharm: Research Funding.

Utilization of Fertility Preservation Services By Patients Aged 18-40 Prior to Hematopoietic Cell Transplantation

Introduction Survivors of hematopoietic cell transplantation (HCT) often face infertility later in life due to preparative conditioning regimens that are harmful to reproductive function. Current American Society of Clinical Oncology (ASCO) clinical guidelines on fertility preservation (FP) recommend that all patients who are at risk for infertility due to medical treatment should be referred to a fertility specialist for counseling following diagnosis and preferably prior to the start of treatment. Despite HCT physicians' awareness of standard-of-care services for preserving fertility and the psychosocial sequelae resulting from patients losing their fertility, anecdotal evidence indicates that few patients actually receive FP services. National utilization of FP services prior to HCT is currently unknown. Objective The goal of this retrospective descriptive analysis is to understand commercially insured and covered FP utilization among HCT recipients and describe patterns of engagement in FP services prior to HCT. Methods FAIR Health's national claims database was used to identify HCT recipients and the subgroup of patients who received FP services prior to HCT. Secondary analysis of the FP subgroup included the creation of patient-specific clinical journey timelines that included dates of services associated with diagnosis and procedure codes relevant to HCT and FP (Figure 1). Results There were 411 patients aged 18-40 who received HCT. Only 7.1% (N=29) of the HCT cohort had claims for FP services after diagnosis and prior to receiving HCT. Utilization of FP was most common in younger HCT patients, with 69% (N=20) of the FP subgroup being under age 26. The median time between FP services and HCT was 102 days and patients undergoing autologous HCT had longer intervals between FP services and HCT than allogeneic HCT patients (Figure 2). Conclusion Despite ASCO guidelines addressing the importance of FP options for cancer patients, results from this administrative claims analysis confirm that utilization of FP services by HCT patients is low. The longitudinally-linked claims allowed for detailed analysis of the FP subgroup which helped inform when patients receive FP services relative to their HCT as well as which FP services are utilized. Analysis of the FP subgroup also showed that the timing between diagnosis, FP services, and HCT may depend on the type of transplant. However, more research is needed to understand the barriers to FP prior to HCT so that targeted tools can be used to increase utilization and improve quality of life for HCT survivors. Future FP service cost and utilization research with an expanded population would be informative for policy-makers, payers, providers and patients. More work is needed to address the difficulty in quantifying FP service utilization that is not processed through commercial payers and as such not included in administrative claims data.

Nilotinib combined with multi-agent chemotherapy in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center prospective study with long-term follow-up.

The aim of this study is to investigate the efficacy and safety of nilotinib combined with multi-agent chemotherapy in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Thirty patients with Ph+ ALL were recruited. Standard induction chemotherapy was given for 4weeks. Nilotinib was administered beginning on day 15 of induction. After achieving hematologic complete remission (HCR), patients received either seven courses of consolidation or hematopoietic cell transplantation (HCT). Nilotinib was continued 2years after achieving HCR or before stem cell transplantation conditioning. HCR and molecular complete response (MCR), overall survival (OS), hematologic relapse-free survival (HRFS), molecular relapse-free survival (MRFS), toxicity, and nilotinib levels in the serum and cerebrospinal fluid were evaluated. All patients achieved HCR, and cumulative MCR rate was 83.3%. The median HRFS and OS were 18 and 47.5months, respectively. Four-year HRFS and OS rates were 54% and 45%, respectively. The median MRFS and 4-year MRFS for the patients with MCR were 19months and 45%, respectively. The molecular response of patients after induction cycle had no impact on HRFS, MRFS, or OS. The patients who achieved MCR after 3 and 6months had superior HRFS. The HCT cohort in the first HCR had significantly lower rates of relapse and longer MRFS, HRFS, and OS. Most adverse events were reversible with dose reduction or transient interruption of nilotinib therapy. Only traces of nilotinib were detected in cerebrospinal fluid. Nilotinib combined with cytotoxic chemotherapy was effective and translated to a high HCR and MCR for patients with Ph+ ALL. It should be noted that nilotinib cannot cross the blood-brain barrier.

Hematopoietic Cell Transplantation and Utilization of Fertility Preservation Services.

Conditioning regimens for hematopoietic cell transplantation (HCT) are harmful to reproductive function, but national utilization of fertility preservation (FP) before HCT has not been studied. The primary aim of this descriptive retrospective analysis is to understand FP utilization in the HCT population of patients between ages 18 and 40 years, whereas the secondary aim is to describe temporal trends in FP before HCT. Key dates, procedures codes, and diagnosis codes were extracted from administrative and health services commercial claims data, which were obtained from FAIR Health's national claims database, to construct 29 patient-specific clinical journey timelines detailing the time from diagnosis to FP and to HCT. Patient characteristics studied include sex, age, HCT type (autologous and allogeneic), and census region. Key findings from primary and secondary analyses were that 7% of the HCT cohort had claims for FP services, FP utilization before HCT decreased with increasing age, there were 102 days (median) between FP and HCT procedure date, and 7 of 29 patients who received FP services had a nonmalignant primary indication for HCT. More research is needed to understand the barriers to FP before HCT so that targeted tools can be used to increase utilization and improve quality of life for HCT survivors.

Adolescent and Young Adult (AYA) Hematopoietic Cell Transplantation (HCT) Recipients Have Similar Quality of Life (QoL) Compared to Older Adults in the First Year Post-Transplantation

▪Background: HCT is physically and psychologically challenging and patients are prone to QoL impairments. AYAs are a unique population that faces hurdles due to dynamic changes in several aspects of their life, and may be particularly prone to QoL issues during HCT. The aim of this study was to determine if QoL differences exist between AYA and older adult HCT recipients pre- and post-HCT. Additionally, we aimed to determine if there has been a change in QoL for AYA transplant recipients in recent years, as more focus has been placed on supporting this unique population.Methods: QoL data were collected prospectively pre-HCT (baseline [BL]) and in follow-up post-transplant on patients undergoing HCT from Jun 2003 through Dec 2017 at Cleveland Clinic. Autologous HCT recipients are followed routinely through day +42 post-transplant, while allogeneic recipients are followed through at least one year or more. QoL was self-reported by patients using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) questionnaire. FACT-BMT consists of five domain scores (Physical Wellbeing [PWB], Social Wellbeing [SWB], Emotional Wellbeing [EWB], Functional Wellbeing [FWB], and Additional Concerns [AC]) and two summary scores (trial outcome index [TOI, PWB+FWB+AC], and Total FACT Score. Scores were compared for younger AYA (age 15-29 years), older AYA (age 30-39 years) and older adults (age 40-60 years). We excluded patients >60 years from analysis as this group may have their own unique challenges. Repeated measures analysis of variance was used to assess differences among age groups and among time points. Pearson correlation (r) was used to determine if BL QOL had improved from 2003-2017 in AYA cohort. Separate analyses were performed for autologous and allogeneic cohorts.Results: Autologous HCT cohort included 128 AYA patients (56 younger AYA) and 355 older adults, and allogeneic HCT cohort included 136 AYA patients (76 younger AYA) and 295 older adults Autologous patients in all three groups were similar for baseline characteristics except for diagnosis (table 1). Among allogeneic patients similar rates of graft-versus host disease were seen for all three groups, and baseline characteristics were similar except for ECOG performance status (table 1). Among autologous recipients, no single QoL domain or composite score differed among the three age groups at baseline or at day +42 post-HCT (Figure 1a). In all age groups, QoL improved from baseline to D+42 in autologous HCT recipients (mean Total Score 149 vs. 152, p=0.001). Similarly, among the allogeneic HCT recipients, no single QoL domain or composite score differed among the three age groups at baseline, day +100, +180, or +365 post-HCT (Figure 1b). Among all patients compared to BL (mean 146), total FACT score improved at day +180 (150, p=0.022) and +365 (152, p=0.005), but not at day 100 (145, p=0.57). Among autologous recipients, none of the BL FACT domains improved over time since 2003. In contrast, AYA allogeneic recipients also had no significant change in BL scores since 2003 for PWB, SWB, EWB, FWB, however there was improvement in AC (r=0.26, p=0.003, TOI (r=0.23, p=0.008), and total FACT score (r=0.19, p=0.03).Conclusions: AYA HCT recipients do not have inferior QoL compared to older adults in the first 42 days after autologous HCT and the first year after allogeneic HCT. Interestingly, QoL improvements in AYA patients have occurred in recent years for allogeneic but not autologous patients. Improvements in QoL of allogeneic patients is driven by the AC domain, which addresses multiple psychosocial aspects which have been emphasized in recent years. Continued efforts to tailor treatment and support for AYA HSCT recipients is critical to improving outcomes. DisclosuresAdvani:Glycomimetics: Consultancy; Novartis: Consultancy; Amgen: Research Funding; Pfizer: Honoraria, Research Funding. Majhail:Atara: Honoraria; Anthem, Inc.: Consultancy; Incyte: Honoraria.

Evolution of Body Composition Following Autologous and Allogeneic Hematopoietic Cell Transplantation: Incidence of Sarcopenia and Association with Clinical Outcomes

Sarcopenia, the loss of muscle mass, has been identified as a potential risk factor for adverse outcomes in hematopoietic cell transplantation (HCT) recipients. However, much remains unknown about change in body composition following HCT. We retrospectively evaluated computed tomography (CT) imaging from 315 lymphoma patients undergoing HCT at our institution between 2000 and 2014. Cross-sectional areas of lean muscle, subcutaneous adipose tissue, and visceral adipose tissue were measured on CT at the level of the third lumbar vertebral body before HCT, 1-year post-HCT, and 2.5 years post-HCT. The incidence of sarcopenia before HCT was 47% in the autologous HCT (auto-HCT) cohort (n = 218) and 55% in the allogeneic HCT (allo-HCT) cohort (n = 97). Older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.04; P < .001) and male sex (OR, 4.59; 95% CI, 1.42 to 4.93; P < .001) were associated with sarcopenia before HCT. Increasing body mass index (OR, .78; 95% CI, .73 to .84; P < .001) was protective against sarcopenia before HCT. A significant decline in total lean body mass (β = 1.96; 95% CI, .79 to 3.13; P = .001) and increased sarcopenia incidence (OR, 1.72; 95% CI, 1.13 to 2.62, P = .012) was observed over time for patients in the allo-HCT cohort when compared with the trend in the auto-HCT cohort. Both auto-HCT and allo-HCT recipients experienced an increase in total body fat mass over time (β = 3.75; 95% CI, 2.77 to 4.73; P < .001). In multivariate analysis of patients undergoing allo-HCT, the presence of sarcopenia on baseline imaging before HCT was associated with a lower risk of acute graft-versus-host disease (OR, .30; 95% CI, .09 to .98; P = .047). In conclusion, we found that total body fat mass increases after both auto-HCT and allo-HCT. Following allo-HCT, total lean body mass significantly decreases corresponding to increased incidence of sarcopenia. Future studies are needed to further characterize changes in body composition in HCT recipients and investigate its impact on HCT outcomes.

Pediatric Hematopoietic Cell Transplant Patients Who Survive Critical Illness Frequently Have Significant but Recoverable Decline in Functional Status

The number of pediatric hematopoietic cell transplant (HCT) patients who survive pediatric intensive care unit (PICU) admission is increasing, yet little is known about their functional morbidity after PICU discharge. We hypothesized that relative to control subjects, pediatric HCT patients who survive PICU admission would have greater rates of new functional morbidity at the time of PICU discharge and only some of these patients would return to their functional baseline by the end of the hospitalization. We performed a retrospective cohort study with secondary data analysis of the Trichotomous Outcomes in Pediatric Critical Care dataset. The pediatric HCT cohort was identified by querying International Classification of Diseases, 9th edition, diagnostic codes. A control group consisted of previously healthy patients matched 4:1 on age, sex, and illness severity, as estimated by the Pediatric Risk of Mortality (PRISM) score. We benchmarked our findings by comparing with a previously healthy group of children with lower respiratory tract infections. Functional impairment was measured by the Functional Status Scale, wherein new morbidity was defined as an increase of ≥3 points relative to the prehospital baseline. Relative to matched control subjects, HCT patients had similar admission PRISM scores (P = .516) but greater PICU mortality (12.9% [11/85] versus 6.2% [21/340], P = .035). However, among those who survived to PICU discharge, HCT patients had similar rates of new morbidity at PICU discharge (14.9% [11/74] versus 17.2% [55/319], P = .622) and similar rates of resolution of new morbidity by hospital discharge (54.5% [6/11] versus 60.0% [33/55], P = .737). Relative to the comparison group with lower respiratory tract infections, HCT patients had both greater admission PRISM scores (P < .001) and greater PICU mortality (12.9% [11/85] versus 1.6% [5/308], P < .001). However, among those who survived to PICU discharge, HCT patients again displayed similar rates of new morbidity at PICU discharge (14.9% [11/74] versus 22.1% [67/303], P = .168) as well as resolution of new morbidity by hospital discharge (54.5% [6/11] versus 71.6% [48/67], P = .299). For pediatric HCT patients PICU survival with new functional morbidity is as prevalent an outcome as PICU mortality. Although pediatric HCT patients have greater PICU mortality than age-, sex-, and PRISM-matched control subjects, they have similar rates of new functional morbidity at PICU discharge and similar resolution of new functional morbidity at hospital discharge. Future interventions focused on improving functional status in pediatric HCT survivors of critical illness are warranted.

Personalized home-based interval exercise training may improve cardiorespiratory fitness in cancer patients preparing to undergo hematopoietic cell transplantation.

Impaired cardiorespiratory fitness is associated with inferior survival in patients preparing to undergo hematopoietic cell transplantation (HCT). Exercise training based on short, higher-intensity intervals has the potential to efficiently improve cardiorespiratory fitness. We studied home-based interval exercise training (IET) in 40 patients prior to autologous (N=20) or allogeneic (N=20) HCT. Each session consisted of 5, three-minute intervals of walking, jogging, or cycling at 65-95% maximal heart rate (MHR) with 3 minutes of low intensity exercise (<65% MHR) between intervals. Participants were asked to perform sessions at least 3 times weekly. The duration of the intervention was at least 6 weeks, depending on each patient’s scheduled transplantation date. Cardiorespiratory fitness was assessed from a peak oxygen consumption test (VO2peak) and a 6 minute walk (6MWD) before and after the intervention period. For the autologous HCT cohort, improvements in VO2peak (p=0.12) and 6MWD (p=0.19) were not statistically significant. For the allogeneic cohort, the median VO2peak improvement was 3.7ml/kg*min (p=0.005) and the median 6MWD improvement was 34 meters (p=0.006). Home-based, interval exercise training can be performed prior to HCT and has the potential to improve cardiorespiratory fitness.

Superiority of Pediatric Chemotherapy over Allogeneic Hematopoietic Cell Transplantation for Philadelphia Chromosome Negative Adult ALL in First Complete Remission: A Combined Analysis of Dana-Farber ALL Consortium and CIBMTR Cohorts

▪Introduction: In adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL), the optimal post-remission therapy remains uncertain. Although allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR1) has become a widely adopted curative strategy, the need for HCT may be supplanted by intensive, pediatric-style chemotherapy regimens. These two approaches have not previously been compared.Methods: We evaluated the outcomes of 422 related or unrelated donor HCT recipients aged 18-50 years with Ph-ALL in CR1 between 06/2002 and 12/2011 as reported to the CIBMTR. This was compared to a concurrent cohort of 108 Ph- ALL CR1 pts (18-50 years) who received a Dana Farber Cancer Institute (DFCI) ALL Consortium pediatric regimen consisting of intensive, non-HCT therapy. Primary outcome was disease-free survival (DFS). Patients in the DFCI chemotherapy cohort who received HCT in CR1 were censored at the day of HCT. Left-truncated analysis methods were used to adjust time from CR1 to transplant.Results: The HCT cohort was older (median age 34 vs. 30 years, p=0.001) and had higher diagnostic WBC counts (median 12x109/L [range <1-515) vs. 8x109/L [1-1424], p=0.001, respectively). The proportion of patients with T –ALL was lower in the HCT cohort (14% vs. 22%, p=0.03), while the incidence of t(4;11)/MLL was similar in both groups (8% vs. 10%, respectively). Of the HCT cohort 396 (94%) underwent myeloablative (MA) conditioning. Donor source was matched related donor in 176 (42%), 8/8 unrelated donors in 168 (40%), and 7/8 (18%) from 7/8 unrelated donors. In univariate analyses (Figure 1) cumulative incidence of relapse at 4 years was similar in both groups (HCT 25% [19-28] vs. chemo 23% [15-32] p=0.97). Two-year treatment-related mortality (TRM) was higher in the HCT cohort (HCT 33% [28-39] vs. chemo 4% [1-8], p<0.0001). At 4 years, DFS was superior in the chemo cohort (HCT 40% [35-45] vs. chemo 71% [60-79], p<0.0001). Four year OS also favored chemo (HCT 45% [40-50] vs. chemo 73% [63-81], p<0.0001). In multivariable analysis, independent factors predictive of treatment failure (relapse or death) were HCT (HR 3.11 [2.08 – 4.66], p<0.001) and the presence of CNS disease at diagnosis (HR 1.56 [1.03 – 2.38], p=0.04). The sole factor associated with poorer OS was the administration of HCT (HR 2.86 [1.88 – 4.34], p<0.0001). The favorable OS with chemo was maintained when restricting the HCT cohort to those recipients with related donors or fully matched (8/8) unrelated donors and those whose time from diagnosis to CR1 was <8 weeks (HR 2.14 [1.36-3.35], p=0.001). Similar outcomes were seen when restricting the HCT cohort to those who achieved CR1 < 8 weeks from diagnosis and received myeloablative conditioning.Conclusion: In this comparison of two cohorts of younger Ph- negative adults in CR1, post-remission therapy with an intensive, pediatric-inspired, chemotherapy-based regimen conferred a survival advantage when compared to allogeneic HCT. The high TRM associated with HCT is a major factor in determining outcomes after HCT. In an era of increasing adoption of pediatric regimens for adults with Ph- ALL, allogeneic HCT may no longer be required for the majority of patients who achieve CR1. These data support the need for randomized controlled studies in Ph- ALL comparing pediatric-inspired non-HCT regimens to allogeneic HCT-based therapy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.