-
1.
A phase II randomized, placebo-controlled, multicenter trial to evaluate the efficacy of cytomegalovirus PepVax vaccine in preventing cytomegalovirus reactivation and disease after allogeneic hematopoietic stem cell transplant
Nakamura, R., La Rosa, C., Yang, D., Hill, J. A., Rashidi, A., Choe, H., Zhou, Q., Lingaraju, C. R., Kaltcheva, T., Longmate, J., et al
Haematologica. 2024
Abstract
Not available.
-
2.
Prediction of Coronary Heart Disease Events in Blood or Marrow Transplantation Recipients
Gangaraju, R., Chen, Y., Hageman, L., Landier, W., Balas, N., Ross, E., Francisco, L., Bosworth, A., Te, H. S., Wong, F. L., et al
JACC. CardioOncology. 2023;5(4):504-517
Abstract
BACKGROUND The long-term risk of coronary heart disease (CHD) and clinical models that predict this risk remain understudied in blood or marrow transplantation (BMT) recipients. OBJECTIVES This study sought to examine the risk of CHD after BMT and identify the associated risk factors. METHODS Participants included patients transplanted between 1974 and 2014 at City of Hope, University of Minnesota, or University of Alabama at Birmingham and those who survived ≥2 years after BMT. Multivariable logistic regression models assessed CHD risk in BMT survivors compared with a sibling cohort. A self-reported questionnaire and medical records provided information regarding sociodemographics, comorbidities, and therapeutic exposures, which were used to develop a CHD risk prediction nomogram. RESULTS Overall, 6,677 BMT recipients participated; the mean age at BMT was 43.9 ± 17.7 years, 58.3% were male, and 73.3% were non-Hispanic Whites. The median length of follow-up was 6.9 years (range: 2-46.2 years) from BMT. CHD was reported in 249 participants, with a 20-year cumulative incidence of 5.45% ± 0.39%. BMT survivors had a 1.6-fold greater odds of CHD compared with a sibling cohort (95% CI: 1.09-2.40). A nomogram was then developed to predict the risk of CHD at 10 and 20 years after BMT including age at BMT (HR: 1.06/y; 95% CI: 1.04-1.08), male sex (HR: 1.89; 95% CI: 1.15-3.11), a history of smoking (HR: 1.61; 95% CI: 1.01-2.58), diabetes (HR: 2.45; 95% CI: 1.23-4.89), hypertension (HR: 2.02; 95% CI: 1.15-3.54), arrhythmia (HR: 1.90; 95% CI: 0.89-4.06), and pre-BMT chest radiation (yes vs no: HR: 2.83; 95% CI: 1.20-6.67; unknown vs no: HR: 0.88; 95% CI: 0.34-2.28). The C-statistic was 0.77 in the test set (95% CI: 0.70-0.83). CONCLUSIONS This study identified BMT recipients at high risk for CHD, informing targeted screening for early detection and aggressive control of risk factors.
-
3.
Sirolimus is an acceptable alternative to tacrolimus for graft-versus-host disease prophylaxis after haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide
Elmariah, H., Otoukesh, S., Kumar, A., Ali, H., Arslan, S., Shouse, G., Pourhassan, H., Nishihori, T., Faramand, R., Mishra, A., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy), tacrolimus (TAC) and mycophenolate mofetil (MMF) for allogeneic haploidentical donor (haplo) hematopoietic cell transplantation (HCT) results in comparable outcomes to matched unrelated donor transplantation. A phase II study from Moffitt Cancer Center substituting sirolimus (SIRO) in place of TAC reported comparable rates of grade II-IV acute GVHD. Many centers have substituted SIRO for TAC in this setting based on a preferred side effect profile, though comparative data is limited. OBJECTIVE The objective of this study is to compare outcomes of haplo HCT with PTCy/SIRO/MMF versus PTCy/TAC/MMF. STUDY DESIGN We retrospectively compared haplo HCT outcomes with PTCy/SIRO/MMF versus PTCy/TAC/MMF. Included were all consecutive patients receiving haplo donor T cell replete peripheral blood stem cell graft HCT for hematologic malignancies at Moffitt Cancer Center or the City of Hope National Medical Center between 2014 and 2019. RESULTS A total of 423 patients were included, of which 84 (20%) received SIRO and 339 (80%) received TAC. Median age for all patients was 54 (range 18 to 78) years, and median follow-up for entire study cohort was 30 months. SIRO group had a higher proportion of patients ≥60 years (58% versus 34%, P = <.01), and the groups also differed in diagnosis type, conditioning regimen, and cytomegalovirus serostatus. There were no significant differences in the rates of grade II-IV acute GVHD (45% versus 47%, P = .6) at day +100 or chronic GVHD (47% versus 54%, P = .79) at 2 years post-HCT. In multivariate analysis, neutrophil engraftment at day +30 was significantly better with TAC (OR = 0.30, CI 0.1 to 0.83, P = .02) with a median time to engraftment of 17 days versus 18 days for SIRO, but platelet engraftment was similar in both groups. Otherwise, in multivariate analysis, GVHD prophylaxis type had no significant influence on acute or chronic GVHD, nonrelapse mortality, relapse, GVHD-free relapse-free survival, disease free survival, or overall survival after peripheral blood haplo HCT. CONCLUSIONS These findings suggest that SIRO is a comparable alternative to TAC in combination with PTCy/MMF for GVHD prophylaxis, resulting in overall similar clinical outcomes despite delay in engraftment after peripheral blood haplo HCT. While TAC remains the standard of care, SIRO may be substituted based on the side effect profile of these medications with consideration of patient medical comorbidities at HCT.
-
4.
Risk of COVID-19 Infection in Long-term Survivors of Blood or Marrow Transplantation: A BMTSS Report
Johnston, E. E., Meng, Q., Hageman, L., Wu, J., Ross, E. S., Lim, S., Balas, N., Bosworth, A. K., Te, H. S., Francisco, L., et al
Blood advances. 2023
Abstract
There is limited information regarding COVID-19 in long-term blood or marrow transplant (BMT) survivors. We leveraged the BMT Survivor Study (BMTSS) to address this gap. BMTSS included patients who underwent BMT at one of three US sites between 1974 and 2014 and survived ≥2 years after BMT. A sibling cohort serves as a non-BMT comparison group. Participants (2,430 BMT survivors; 780 non-BMT participants) completed the BMTSS survey between 10/2020 and 11/2021 about COVID-19 testing, risk mitigation behaviors, morbidity, and healthcare utilization. Median age at BMT was 46 years (range: 0-78 years) and median follow up since BMT was 14 years (6-46 years); 76% were non-Hispanic white, 54% had received allogeneic BMT. The risk of COVID-19 infection was comparable for BMT survivors vs non-BMT participants (15-month cumulative incidence: 6.5% vs. 8.1%; adjusted odd ratio [aOR]=0.93, 95%CI=0.65-1.33, p=0.68). Among survivors, being unemployed (aOR=1.90, 95%CI=1.12-3.23, p=0.02; reference: retired) increased the odds of infection; always wearing a mask in public was protective (aOR=0.49, 95%CI=0.31-0.77. p=0.002; reference: not always masking). When compared with COVID positive non-BMT participants, COVID positive BMT survivors had higher odds of hospitalization (aOR=2.23, 95%CI=0.99-5.05, p=0.05); however, the odds of emergency department visits were comparable (aOR=1.60, 95%CI=0.71-3.58, p=0.25). COVID-19 infection status did not increase the odds of hospitalization among BMT survivors (aOR=1.32, 95%CI=0.89-1.95, p=0.17, but did increase the odds of ED visits (aOR=2.63, 95%CI=1.74-3.98, p=<0.0001). These findings inform healthcare providers about the management of long-term BMT survivors during the ongoing pandemic.
-
5.
Feasibility of implementing a supervised telehealth exercise intervention in frail survivors of hematopoietic cell transplantation: a pilot randomized trial
Lee, K., Shamunee, J., Lindenfeld, L., Ross, E., Hageman, L., Sedrak, M. S., Wong, F. L., Nakamura, R., Forman, S. J., Bhatia, S., et al
BMC cancer. 2023;23(1):390
Abstract
BACKGROUND Patients undergoing hematopoietic cell transplantation (HCT) are at high risk of chronic health complications, including frailty and physical dysfunction. Conventional exercise programs have been shown to improve frailty in other cancer populations, but these have largely been based out of rehabilitation facilities that may act as geographic and logistical barriers. There is a paucity of information on the feasibility of implementing telehealth exercise interventions in long-term HCT survivors. METHODS We conducted a pilot randomized trial to assess the feasibility of an 8-week telehealth exercise intervention in 20 pre-frail or frail HCT survivors. Participants were randomized to either a telehealth exercise (N = 10) or delayed control (N = 10). We administered a remote physical function assessment at baseline, followed by an 8-week telehealth exercise intervention (30-60 min/session, 3 sessions/week), and post-intervention. The primary endpoint was feasibility as determined by 1) > 70% of participants completing all remote physical functional assessments, and 2) > 70% of participants in the exercise group completing > 70% (17/24) of the prescribed exercise sessions. Exploratory outcomes included changes in gait speed, handgrip strength, and short physical performance battery. RESULTS The mean [standard deviation] age at study enrollment was 64.7 [9.1] years old. Twelve had undergone allogenic and 8 had undergone autologous HCT at an average of 17 years from study enrollment. Both feasibility criteria were achieved. Nineteen patients (95%) completed all remote study outcome assessments at baseline and post-intervention, and nine participants in the exercise group completed > 70% of prescribed exercise sessions. Overall, no significant group x time interaction was observed on handgrip strength, fatigue, body mass index, and short physical performance battery test (P < 0.05). However, there were significant within-group improvements in four-meter gait speed (+ 13.9%; P = 0.004) and 5-minute gait speed (+ 25.4%; P = 0.04) in the exercise group whereas non-significant changes in four-meter gait speed (-3.8%) and 5-minute gait speed (-5.8%) were observed after 8 weeks. CONCLUSION Implementing an 8-week telehealth exercise intervention for long-term HCT survivors was feasible. Our findings set the stage for innovative delivery of supervised exercise intervention that reduces the burden of frailty in HCT survivors as well as other at-risk cancer survivors. TRIAL REGISTRATION The protocol and informed consent were approved by the institutional IRB (IRB#20731) and registered (ClinicalTrials.gov NCT04968119; date of registration: 20/07/2021).
-
6.
Tocilizumab for Cytokine Release Syndrome Management after Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis
Yao, J. M., Otoukesh, S., Kim, H., Yang, D., Mokhtari, S., Samara, Y., Blackmon, A., Arslan, S., Agrawal, V., Pourhassan, H., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Cytokine release syndrome (CRS) is a common complication after haploidentical hematopoietic cell transplant (HaploHCT). Severe CRS after haploHCT leads to higher risk of non-relapse mortality (NRM) and worse overall survival (OS). Tocilizumab (TOCI) is an interleukin-6 receptor inhibitor and is commonly used as first-line for CRS management after chimeric antigen receptor T cell therapy, but the impact of TOCI administration for CRS management on Haplo HCT outcomes is not known. OBJECTIVES In this single center retrospective analysis, we compared HCT outcomes in patients treated with or without TOCI for CRS management after HaploHCT with post-transplant cyclophosphamide- (PTCy-) based graft-versus-host disease (GVHD) prophylaxis. STUDY DESIGN Of the 115 patients eligible patients who underwent HaploHCT at City of Hope between 2019 to 2021 and developed CRS, we identified 11 patients who received tocilizumab for CRS management (TOCI). These patients were matched with 21 patients who developed CRS but did not receive tocilizumab (NO-TOCI) based on age at the time of HCT (≤64 years or >65 years or older), conditioning intensity (MAC vs RIC/NMA), and CRS grading (1, 2 vs 3-4). Instead of 22 controls, we chose 21 patients because there was only one control matched with one TOCI treatment patient in one stratum. With only 11 patients in receiving tocilizumab for CRS treatment, matching with 21 patients who developed CRS but did not receive tocilizumab, we had 80% power to detect big differences (HR=3.4 or higher) in transplant outcomes using a two-sided 0.05 test. The power would be reduced to about 20-30% if the difference was moderate (HR=2.0) using the same test. RESULTS No CRS-related deaths were recorded in either group. Median time to neutrophil engraftment was 21 days (range: 16-43) in TOCI and 18 days (range 14-23) in NO-TOCI group (HR=0.55; 95% CI: 0.28-1.06, P=0.08). Median time to platelet engraftment was 34 days (range: 20-81) in TOCI and 28 days (range: 12-94) in NO-TOCI group (HR=0.56; 95% CI: 0.25-1.22, P= 0.19). Cumulative incidences of day +100 acute GVHD grades II-IV (P=0.97) and grades III-IV (P=0.47) were similar between the two groups. However, cumulative incidence of chronic GvHD at 1 year was significantly higher in patients receiving TOCI (64% vs 24%; P=0.05). Rates of NRM (P=0.66), relapse (P=0.83), disease-free survival (P=0.86), and overall survival (P=0.73) were similar at 1-year post-HCT between the two groups. CONCLUSIONS Tocilizumab administration for CRS management after HaploHCT appears to be safe with no short-term adverse effect and no effect on relapse rate. However, the significantly higher cumulative incidence of chronic GvHD, negates the high efficacy of PTCy on GvHD prophylaxis in this patient population. Therefore, using tocilizumab for CRS management in the HaploHCT population with PTCy maybe kept only for patients with severe CRS. The impact on such approach on long term outcome in HaploHCT with PTCy will need to be evaluated in a larger retrospective study or a prospective manner.
-
7.
Risky Health Behaviors and Subsequent Late Mortality after Blood or Marrow Transplantation: a BMTSS Report
Balas, N., Richman, J., Landier, W., Shrestha, S., Bruxvoort, K., Hageman, L., Meng, Q., Ross, E. S., Bosworth, A. K., Te, H. S., et al
Blood advances. 2023
Abstract
We examined the association between risky healthy behaviors (smoking, heavy-alcohol consumption, and lack of vigorous-physical activity) and all-cause and cause-specific late mortality after blood or marrow transplantation (BMT) to understand the role played by potentially modifiable risk factors. Study participants were drawn from the BMT Survivor Study (BMTSS), and included patients transplanted between 1974 and 2014, who had survived ≥2 years post BMT and were age ≥18 at study cohort entry. Survivors provided information on sociodemographic characteristics, chronic health conditions and health-behaviors. National Death Index was used to determine survival and cause of death. Multivariable regression analyses determined the association between risky health behaviors and all-cause mortality (Cox regression) and non-recurrence related mortality [NRM] (sub-distribution hazard regression) after adjusting for relevant sociodemographic, clinical variables and therapeutic exposures. Overall, 3,866 participants completed the BMTSS survey and were followed for a median of 5 years to death or December 31, 2021; 856 participants died (22.1%) after survey completion. Risky health behaviors were associated with increased hazard of all-cause mortality (adjusted hazard ratio [aHR] former smoker=1.2, aHR current smoker=1.7, ref: non-smoker; aHR heavy drinker=1.4; ref: non-heavy drinker; and aHR no vigorous activity=1.2, ref: vigorous activity) and NRM (aHR former smoker=1.3, aHR current smoker=1.6, ref: non-smoker; aHR heavy drinker=1.4; ref: non-heavy drinker; and aHR no vigorous activity=1.2, ref: vigorous activity). The association between potentially modifiable risky health behaviors and late mortality offers opportunities for development of interventions to improve both the quality and quantity of life after BMT.
-
8.
Post-transplant sinusoidal obstruction syndrome in adult patients with B-cell Acute Lymphoblastic Leukemia treated with pre-transplant Inotuzumab
Agrawal, V., Pourhassan, H., Tsai, N. C., Ngo, D., Koller, P., Malki, M. M. A., Salhotra, A., Ali, H., Aribi, A., Sandhu, K. S., et al
Transplantation and cellular therapy. 2023
Abstract
Sinusoidal obstruction syndrome (SOS) is potentially a life-threatening complication that can be observed after allogeneic hematopoietic cell transplantation (HCT). Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody-drug conjugate that has demonstrated high efficacy in relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL), however, it is associated with increased risk of SOS among transplant recipients. Here, we aimed to examine the incidence and outcomes of SOS in 47 adult patients with R/R ALL that received inotuzumab and subsequently underwent HCT at our institution. All patients received prophylactic therapy with ursodiol, and continuous low dose heparin was administered as well to patients receiving myeloablative conditioning. SOS occurred in 12 (26%) patients post-HCT, with a median onset of 11 days (range: 3-41). SOS was graded as very severe in 50% (n=6), severe in 25% (n=3), and mild in 25% (n=3). All patients diagnosed with SOS received treatment with defibrotide for a median of 21 days (range: 3-34), with resolution of SOS in 67% (n=8) of patients. Mortality rate from SOS was 33% (n=4) and occurred with a median of 10 days from diagnosis (range: 3-31), and in patients graded as very severe (n=3) or severe (n=1). No significant difference in median duration between the last dose of inotuzumab and transplant (46 vs. 53 days, P=0.37), the use of myeloablative conditioning regimen (42% vs. 49%, P=0.75), number of lines of therapy prior to inotuzumab (P=0.79), the median number of administered cycles of inotuzumab (2 vs. 2, P=0.14), or receiving inotuzumab as the last therapy prior to HCT (67% vs. 66%, P=1.0) was observed between patients who did and did not develop SOS, respectively. Sirolimus-based graft versus host disease (GVHD) prophylaxis was utilized more frequently in the SOS group (75% vs. 29%, P<0.01), but there were no differences in the peak sirolimus level (P=0.81) or the median time to peak sirolimus level (7 vs. 3.5 days, P=0.39) between the two subgroups, respectively. In univariable analysis, only the use of sirolimus-based GVHD prophylaxis was significantly associated with increased risk of SOS (HR=7.50 [95% CI:1.7-33.6, P<0.01]). In the SOS group, the 100-day mortality rate was 33% (n=4) and median overall survival (OS) post-HCT of 4.3 months (range: 0.2 - 57.2). In the group without SOS, the 100-day mortality rate was 14% (n=5) and the median OS post-HCT was 10.7 months (range: 0.52 - 39.6). Here, we showed that SOS is prevalent in transplant recipients who were treated with inotuzumab prior to transplant, and that sirolimus-based GVHD prophylaxis was a risk factor for SOS in inotuzumab recipients in our cohort.
-
9.
The impact of SARS-CoV2 vaccines on the incidence of graft versus host disease in allogeneic hematopoietic stem cell transplant recipients: a single-center retrospective study
Ngo, D., Chen, J., Tinajero, J., Aribi, A., Arslan, S., Marcucci, G., Nakamura, R., Al Malki, M. M., Forman, S. J., Dadwal, S., et al
Stem cell research & therapy. 2023;14(1):95
Abstract
This study reports the incidence of chronic graft versus host disease (GvHD) in allogeneic hematopoietic stem cell transplant (alloHCT) recipients who received SARS-CoV2 vaccination. The overall rates of new and worsening chronic GvHD combined were 14%, with median time from vaccination to GVHD being approximately three to four weeks. A majority of the cases were of mild to moderate severity and primarily localized to either the skin, mouth, or joints. Prior chronic GVHD and recent transplant were associated with higher GVHD rates following COVID-19 vaccination. More prospective studies are needed to provide a definitive mechanism for the impact of SARS-CoV2 vaccination on alloHCT patients.
-
10.
Clonal Hematopoiesis and Cardiovascular Disease in Patients With Multiple Myeloma Undergoing Hematopoietic Cell Transplant
Rhee, J. W., Pillai, R., He, T., Bosworth, A., Chen, S., Atencio, L., Oganesyan, A., Peng, K., Guzman, T., Lukas, K., et al
JAMA cardiology. 2023
-
-
Free full text
-
Abstract
IMPORTANCE There is a paucity of information on the association between clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular disease (CVD) in patients with cancer, including those with multiple myeloma (MM) undergoing hematopoietic cell transplant (HCT), a population at high risk of developing CVD after HCT. OBJECTIVE To examine the association between CHIP and CVD in patients with MM and to describe modifiers of CVD risk among those with CHIP. DESIGN, SETTING, AND PARTICIPANTS This was a retrospective cohort study of patients with MM who underwent HCT between 2010 and 2016 at City of Hope Comprehensive Cancer Center in Duarte, California, and had pre-HCT mobilized peripheral blood stem cell (PBSC) products cryopreserved and accessible for CHIP analyses. The study team performed targeted panel DNA sequencing to detect the presence of CHIP (variant allele frequency 2% or more). MAIN OUTCOMES AND MEASURES The primary end point was the 5-year cumulative incidence and risk for developing de novo CVD (heart failure, coronary artery disease, or stroke) after HCT. RESULTS Of 1036 consecutive patients with MM (580 male [56%]; median age, 60.0 years) who underwent a first autologous HCT, 201 patients had at least 1 CHIP variant (19.4%) and 35 patients had 2 or more variants (3.4%). The 5-year incidence of CVD was significantly higher in patients with CHIP (21.1% vs 8.4%; P < .001) compared with those without CHIP; the 5-year incidence among those with 2 or more variants was 25.6%. In the multivariable model, CHIP was associated with increased risk of CVD (hazard ratio [HR], 2.72; 95% CI, 1.70-4.39), as well as of individual outcomes of interest, including heart failure (HR, 4.02; 95% CI, 2.32-6.98), coronary artery disease (HR, 2.22; 95% CI, 1.06-4.63), and stroke (HR, 3.02; 95% CI, 1.07-8.52). Patients who had both CHIP and preexisting hypertension or dyslipidemia were at nearly 7-fold and 4-fold increased risk of CVD, respectively (reference: no CHIP, no hypertension, or dyslipidemia). CONCLUSION AND RELEVANCE CHIP was significantly and independently associated with risk of CVD in patients with MM undergoing HCT and may serve as a novel biologically plausible biomarker for CVD in this cohort. Patients with MM and both CHIP and cardiovascular risk factors had an exceptionally high risk of CVD. Additional studies are warranted to determine if cardiovascular preventive measures can reduce CHIP-associated CVD risk.