Publications by authors named "Navneet S Majhail"

229 Publications

The Similarity of Class II HLA Genotypes Defines Patterns of Autoreactivity in Idiopathic Bone Marrow Failure Disorders.

Blood 2021 Nov 5. Epub 2021 Nov 5.

Cleveland Clinic, Cleveland, Ohio, United States.

Idiopathic aplastic anemia (IAA) is a rare autoimmune bone marrow failure disorder initiated by a human leukocyte antigen (HLA)-restricted T cell response to unknown antigens. As for other autoimmune disorders, the predilection for certain HLA profiles seems to represent an etiologic factor, however, the structure-function patterns involved in the self-presentation in this disease remain unclear. Herein we analyzed the molecular landscape of HLA complexes of a cohort of 300 IAA patients and almost 3000 healthy and disease controls, by deeply dissecting their genotypic configurations, functional divergence, self-antigen binding capabilities and T cell receptor (TCR) repertoire specificities. Specifically, analysis of the evolutionary divergence of HLA genotypes (HED) showed that IAA patients carried class II HLA molecules whose antigen binding sites were characterized by a high level of structural homology, only partially explained by specific risk allele profiles. This pattern implies reduced HLA binding capabilities, confirmed by binding analysis of hematopoietic stem cell derived self-peptides. IAA phenotype was associated with the enrichment in a few amino acids at specific positions within the peptide binding groove of DRB1 molecules, affecting the interface HLA-antigen-TCR β and potentially constituting the basis of T-cell dysfunction and autoreactivity. When analyzing associations with clinical outcomes, low HED was associated with risk of malignant progression and worse survival, underlying reduced tumor surveillance in clearing potential neoantigens derived from mechanisms of clonal hematopoiesis. Our data shed light on the immunogenetic risk associated with IAA etiology and clonal evolution, and on general pathophysiological mechanisms potentially involved also in other autoimmune disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2021012900DOI Listing
November 2021

The impact of socioeconomic disparities on the use of upfront autologous stem cell transplantation for mantle cell lymphoma.

Leuk Lymphoma 2021 Sep 15:1-9. Epub 2021 Sep 15.

Taussig Cancer Institute, Department of Medical Oncology and Hematology, Cleveland Clinic, Cleveland, OH, USA.

Using the National Cancer Database, we identified 10,290 patients with newly diagnosed mantle cell lymphoma (MCL) treated with chemotherapy with or without upfront autologous stem cell transplantation (ASCT). Only 17% of patients underwent ASCT. Patients who underwent ASCT were younger and more likely to have lower comorbidity scores, private insurance, higher income and education, and treatment received at an academic facility. On multivariable analysis, age, comorbidity index, insurance type, the transition of care, facility type, distance to facility, and diagnosis year were predictive for ASCT use. ASCT use was associated with improved 5-year overall survival in younger (82% vs. 64%,  < .001) and older (70% vs. 40%,  < .001) patients, which was retained in the matched propensity score and 12-month analyses. Female gender, the diagnosis year ≥2009, private insurance, higher income, and education were associated with superior survival, whereas Black race and higher comorbidities predicted inferior survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2021.1978085DOI Listing
September 2021

Image-guided volumetric-modulated arc therapy of total body irradiation: An efficient workflow from simulation to delivery.

J Appl Clin Med Phys 2021 Oct 4;22(10):169-177. Epub 2021 Sep 4.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Introduction: Using multi-isocenter volumetric-modulated arc therapy (VMAT) for total body irradiation (TBI) may improve dose uniformity and vulnerable tissue protection compared with classical whole-body field technique. Two drawbacks limit its application: (1) VMAT-TBI planning is time consuming; (2) VMAT-TBI plans are sensitive to patient positioning uncertainties due to beam matching. This study presents a robust planning technique with image-guided delivery to improve dose delivery accuracy. In addition, a streamlined sim-to-treat workflow with automatic scripts is proposed to reduce planning time.

Materials: Twenty-five patients were included in this study. Patients were scanned in supine head-first and feet-first directions. An automatic workflow was used to (1) create a whole-body CT by registering two CT scans, (2) contour lungs, kidneys, and planning target volume (PTV), (3) divide PTV into multiple sub-targets for planning, and (4) place isocenters. Treatment planning included feathered AP/PA beams for legs/feet and VMAT for the body. VMAT-TBI was evaluated for plan quality, planning/delivery time, and setup accuracy using image guidance.

Results: VMAT-TBI planning time can be reduced to a day with automatic scripts. Treatment time took around an hour per fraction. VMAT-TBI improved dose coverage (PTV V100 increased from 76.8 ± 10.5 to 88.5 ± 2.6; p < 0.001) and reduced lung dose (lung mean dose reduced from 10.8 ± 0.7 Gy to 9.4 ± 0.8 Gy, p < 0.001) compared with classic AP/PA technique.

Conclusion: A VMAT-TBI sim-to-treat workflow with robust planning and image-guided delivery was proposed. VMAT-TBI improved the plan quality compared with classical whole-body field techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acm2.13412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504588PMC
October 2021

Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes.

Transplant Cell Ther 2021 Nov 14;27(11):921.e1-921.e10. Epub 2021 Aug 14.

Department of Hematology/Oncology, Hospital Infantil Universitario Nino Jesus, Madrid, Spain.

Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age ≥60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose ≤7.2 mg/kg or a low-dose melphalan total dose ≤150 mg/m. The 2 groups, recipients of FluBu (n = 697) and recipients of FluMel (n = 448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44% (P ≤ .0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P ≤ .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [P = .02] and 35% versus 27% at 3 years [P = .01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P = .4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P = .03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtct.2021.08.007DOI Listing
November 2021

Not So Young at Heart: Long-Term Cardiac Dysfunction in Young Adult Hematopoietic Cell Transplantation Survivors.

JACC CardioOncol 2020 Sep 15;2(3):472-474. Epub 2020 Sep 15.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaccao.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352283PMC
September 2020

Influence of Killer Immunoglobulin-Like Receptors and Somatic Mutations on Transplant Outcomes in Acute Myeloid Leukemia.

Transplant Cell Ther 2021 Nov 8;27(11):917.e1-917.e9. Epub 2021 Aug 8.

Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Natural killer (NK) cells are regulated by killer immunoglobulin-like receptor (KIR) interactions with human leukocyte antigen class I ligands. Various models of NK cell alloreactivity have been associated with outcomes after allogeneic hematopoietic cell transplant (alloHCT), but results have varied widely. We hypothesized that somatic mutations in acute myeloid leukemia (AML) in the context of KIR profiles may further refine their association with transplant outcomes. In this single-center, retrospective, observational study, 81 AML patients who underwent matched-related donor alloHCT were included. Post-HCT outcomes were assessed based on mutational status and KIR profiles with the Kaplan-Meier method and log-rank test. On multivariable analysis those with any somatic mutations and C1/C2 heterozygosity had less acute graft-versus-host disease (GvHD) (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.14-0.75; P = .009), more relapse (HR, 3.02; 95% CI, 1.30-7.01; P = .010), inferior relapse-free survival (RFS; HR, 2.22; 95% CI, 1.17-4.20; P = .014), and overall survival (OS; HR, 2.21; 95% CI, 1.17-4.20; P = .015), whereas those with a missing KIR ligand had superior RFS (HR, 0.53; 95% CI, 0.30-0.94; P = .031). The presence of a somatic mutation and donor haplotype A was also associated with less acute GvHD (HR, 0.38; 95% CI, 0.16-0.92; P = .032), more relapse (HR, 2.72; 95% CI, 1.13-6.52; P = .025), inferior RFS (HR, 2.11; 95% CI, 1.07-4.14; P = .030), and OS (HR, 2.20; 95% CI, 1.11-4.38; P = .024). Enhanced NK cell alloreactivity from more KIR activating signals (donor B haplotype) and fewer inhibitory signals (recipient missing KIR ligand or C1 or C2 homozygosity) may help mitigate the adverse prognosis associated with some AML somatic mutations. These results may have implications for improving patient risk stratification prior to transplant and optimizing donor selection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtct.2021.08.002DOI Listing
November 2021

Clinical and basic implications of dynamic T cell receptor clonotyping in hematopoietic cell transplantation.

JCI Insight 2021 07 8;6(13). Epub 2021 Jul 8.

Translational Hematology and Oncology Research Program, Department of Hematology and Oncology, Cleveland Clinic, Cleveland, Ohio, USA.

TCR repertoire diversification constitutes a foundation for successful immune reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). Deep TCR Vβ sequencing of 135 serial specimens from a cohort of 35 allo-HCT recipients/donors was performed to dissect posttransplant TCR architecture and dynamics. Paired analysis of clonotypic repertoires showed a minimal overlap with donor expansions. Rarefied and hyperexpanded clonotypic patterns were hallmarks of T cell reconstitution and influenced clinical outcomes. Donor and pretransplant TCR diversity as well as divergence of class I human leukocyte antigen genotypes were major predictors of recipient TCR repertoire recovery. Complementary determining region 3-based specificity spectrum analysis indicated a predominant expansion of pathogen- and tumor-associated clonotypes in the late post-allo-HCT phase, while autoreactive clones were more expanded in the case of graft-versus-host disease occurrence. These findings shed light on post-allo-HCT adaptive immune reconstitution processes and possibly help in tracking alloreactive responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.149080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410023PMC
July 2021

Secular trends of Blood stream infections in allogeneic hematopoietic cell transplant recipients 72 hours prior to death.

Transpl Infect Dis 2021 Aug 18;23(4):e13631. Epub 2021 May 18.

Department of Infectious Diseases, Respiratory Institute Cleveland Clinic, Cleveland, OH, USA.

Introduction: Blood stream infections (BSI) frequently cause morbidity and mortality in allogeneic (allo) hematopoietic cell transplant (HCT) recipients. Characteristics of causative organisms shortly before death have not been previously described. Early treatment with antimicrobial agents targeting the recent surge in multidrug-resistant (MDR) pathogens may lead to better outcomes.

Methods: This is retrospective study including 529 allo HCT recipients who died between 2000 and 2013. All patients who had BSI that happened 72 hours before death were included. BSI and criteria for antimicrobial resistance were defined according to the Centers for Disease Control and Prevention and the National Healthcare Safety Network surveillance criteria.

Results: Overall, 104 BSI were identified from 91 patients. Bacterial infections accounted for 87% of the infections which were comprised by 37% gram-negative organisms and 50% gram-positive bacteria. The most common species were Enterococcus (30%), Staphylococcus (16%), and Pseudomonas (16%). Most enterococci were vancomycin resistant (87%), 100% of staphylococci were resistant to methicillin, and 64% of Pseudomonas were MDR. Over time there was a significant increase in vancomycin-resistant enterococcal (P = .01) and gram-negative BSI (P = .01). Blood stream infections were either the primary or secondary cause of death in 53% of patients.

Conclusions: In allo HCT recipients, vancomycin-resistant enterococcal infections caused the majority of BSI 72 hours prior to death. Our findings provide information that may guide empiric antibiotic coverage in critically ill HCT recipients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13631DOI Listing
August 2021

Late Effects after Chimeric Antigen Receptor T cell Therapy for Lymphoid Malignancies.

Transplant Cell Ther 2021 03 21;27(3):222-229. Epub 2020 Dec 21.

Taussig Cancer Center, Cleveland Clinic, Cleveland, OH.

Chimeric Antigen Receptor T-cell [CAR T] therapy has changed the treatment landscape of relapsed/refractory lymphoid malignancies. With an expanding pool of post CAR T-cell therapy survivors, prevention and management of late toxicities is emerging as an important component of survivorship care. This review summarizes the current state of evidence on late toxicities after CAR T-cell therapy in lymphoid malignancies. Late effects that are well described in clinical trials and observational studies include hypogammaglobulinemia, prolonged cytopenias, late infections, neurologic and neuropsychiatric effects, immune-related late effects, and subsequent malignancies. Hypogammaglobulinemia is the most common late effect in the setting of CD19-directed CAR T-cell therapy, which necessitates immunoglobulin replacement. Common determinants of late toxicities are age, underlying tumor type, prior therapy, CAR construct, and acute toxicities. Among currently approved indications, the incidence of hypogammaglobulinemia and prolonged cytopenia is higher in patients with acute lymphoblastic leukemia compared to aggressive non-Hodgkin lymphoma. Patient-reported physical and mental quality of life in long-term survivors is comparable to general population, albeit, with limited data thus far. This review provides an overview of the incidence, known risk-factors, and strategies for prevention and management of late toxicities in this population. Further research is needed to characterize the trajectory of late effects from population-based registries and long-term follow-up of ongoing clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtct.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078596PMC
March 2021

Return to Work Among Young Adult Survivors of Allogeneic Hematopoietic Cell Transplantation in the United States.

Transplant Cell Ther 2021 08 22;27(8):679.e1-679.e8. Epub 2021 Apr 22.

Center for International Blood and Marrow Transplant Research), National Marrow Donor Program/Be The Match, Minneapolis, Minnesota.

Young adult (YA) survivors of allogeneic hematopoietic cell transplantation (HCT) are at risk for late psychosocial challenges, including the inability to return to work post-HCT. Work-related outcomes in this population remain understudied, however. We conducted this study to assess the post-HCT work status of survivors of allogeneic HCT who underwent HCT as YAs and to analyze the patient-, disease-, and HCT-related factors associated with their work status at 1 year post-HCT. Using Center for International Blood and Marrow Transplant Research data, we evaluated the post-HCT work status (full-time, part-time work, unemployed, or medical disability) of 1365 YA HCT survivors who underwent HCT between 2008 and 2015. Percentages of work status categories were reported at 4 time points: 6 months, 1 year, 2 years, and 3 years post-HCT. Percentages of post-HCT work status categories at the 1-year time point were also described in relation to survivors' pre-HCT work status categories. Factors associated with 1-year post-HCT work status (full-time or part-time work) were examined using logistic regression. From 6 months to 3 years post-HCT, the percentage of survivors working full-time increased from 18.3% to 50.7% and the percentage working part-time increased from 6.9% to 10.5%. Of patients in full-time work pre-HCT, 50% were unemployed or on medical disability at 1 year post-HCT. Female sex (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.40 to 0.77), HCT Comorbidity Index score ≥3 (OR, 0.57; 95% CI, 0.39 to 0.82), pre-HCT unemployment (OR, 0.37; 95% CI, 0.24 to 0.56), medical disability (OR, 0.44; 95% CI, 0.28 to 0.70), development of grade III-IV acute graft-versus-host disease (OR, 0.52; 95% CI, 0.34 to 0.80), and relapse within 1 year post-HCT (OR, 0.34; 95% CI, 0.21 to 0.56) were associated with a lower likelihood of employment at 1 year post-HCT. Compared with myeloablative conditioning (MAC) with total body irradiation (TBI), MAC without TBI (OR, 1.71; 95% CI, 1.16 to 2.53) was associated with a greater likelihood of employment at 1 year post-HCT. Graduate school-level education (OR, 2.47; 95% CI, 1.49 to 4.10) was also associated with a greater likelihood of employment at 1 year post-HCT. Although the work status among YA HCT survivors continued to improve over time, a substantial subset became or remained unemployed or on medical disability. These findings underscore the need for effective interventions to support return to work in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtct.2021.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425287PMC
August 2021

The Democratization of Scientific Conferences: Twitter in the Era of COVID-19 and Beyond.

Curr Hematol Malig Rep 2021 04 31;16(2):132-139. Epub 2021 Mar 31.

Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Unit 428, PO BOX 301402, Houston, TX, 77230, USA.

Purpose Of Review: The coronavirus disease 2019 (COVID-19) pandemic has had profound impacts upon scientific discourse in our field, most prominently through the abrupt transition of malignant hematology conferences to all-digital formats. These virtual components will likely be incorporated into future iterations of these conferences even as in-person attendance is reincorporated. In this review, we discuss ways in which usage of the social networking platform Twitter has expanded in the past year during virtual conferences as a method to facilitate-and, in some ways, democratize-information flow and professional networking.

Recent Findings: Emerging Twitter-based tools in malignant hematology include presenter-developed #tweetorials, conference-specific "poster walks," and disease-specific online journal clubs. Twitter is also increasingly being used for networking across institutional and international lines, allowing for conversations to continue year-round as a first step toward multicenter collaborations as well as in-person #tweetups at subsequent meetings. The ability of Twitter to enable uninterrupted information exchange has reinforced its central role in medical and scientific communication in a way that will certainly outlive the COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11899-021-00620-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011363PMC
April 2021

Worldwide Network for Blood and Marrow Transplantation (WBMT) Recommendations Regarding Essential Medications Required To Establish An Early Stage Hematopoietic Cell Transplantation Program.

Transplant Cell Ther 2021 03 16;27(3):267.e1-267.e5. Epub 2020 Dec 16.

Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

Establishing a hematopoietic cell transplantation (HCT) program is complex. Planning is essential while establishing such a program to overcome the expected challenges. Authorities involved in HCT program establishment will need to coordinate the efforts between the different departments required to start up the program. One essential department is pharmacy and the medications required. To help facilitate this, the Worldwide Network for Blood and Marrow Transplantation organized a structured survey to address the essential medications required to start up an HCT program. A group of senior physicians and pharmacists prepared a list of the medications used at the different phases of transplantation. These drugs were then rated by a questionnaire using a scale of necessity based on the stage of development of the transplant program. The questionnaire was sent to 30 physicians, in different parts of the world, who have between 5 and 40 years of experience in autologous and/or allogeneic transplantation. This group of experts scored each medication on a 7-point scale, ranging from an absolute requirement (score of 1) to not required (score of 7). The results are presented here to help guide the prioritization of required medications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtct.2020.12.015DOI Listing
March 2021

Outcomes and factors impacting use of axicabtagene ciloleucel in patients with relapsed or refractory large B-cell lymphoma: results from an intention-to-treat analysis.

Leuk Lymphoma 2021 06 29;62(6):1344-1352. Epub 2020 Dec 29.

Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

Data on real-world outcomes of axicabtagene ciloleucel (axi-cel) therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL) are limited. In this intent to treat (ITT) analysis, we reviewed records of 38 consecutive patients with R/R LBCL for whom axi-cel was intended. Twenty-seven (71%) patients received axi-cel and 11 (29%) did not. Patients in the non-axi-cel group had a higher hematopoietic cell transplantation comorbidity index (HCT-CI) (median 4 vs. 2,  = .04). Median overall survival for the ITT, axi-cel and non-axi-cel group was 10 (95% CI, 3.7 to 13), 13 (95% CI, 7.7 to N.R.) and 1 (95% CI, 0.4 to 3.7) month(s) respectively. Factors limiting axi-cel use were disease progression, sepsis, manufacturing failure and socioeconomic barrier in 6 (55%), 3 (27%), 1 (9%) and 1 (9%) patient(s) respectively. Additional strategies are needed to ensure all LBCL patients for whom chimeric antigen receptor (CAR) T-cell therapy is prescribed can receive this treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2020.1864349DOI Listing
June 2021

Survival following relapse after allogeneic hematopoietic cell transplantation for acute leukemia and myelodysplastic syndromes in the contemporary era.

Hematol Oncol Stem Cell Ther 2021 Dec 5;14(4):318-326. Epub 2020 Dec 5.

Blood and Marrow Transplant Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address:

Objective/background: Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). No standard of care exists, and a wide range of treatments are used for post-alloHCT relapse. In the recent era, several novel therapies including targeted agents are available for acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS).

Methods: We reviewed outcomes after alloHCT relapse, with or without use of these newer agents for ALL, AML, and MDS. In total, 115 adults with relapsed or refractory ALL (n = 17), AML (n = 67), and MDS (n = 31) at median 5 (range, 1-64) months after their first alloHCT in 2010-2018 were included.

Results: Median follow-up was 19 (range, 6-80) months after relapse from alloHCT. Targeted agents were given to 29 (25%) patients. In multivariable analysis, use of targeted agent at any time point after relapse was not associated with survival. Matched unrelated (vs. matched sibling; hazard ratio [HR] 1.70; p = .027) or haploidentical donor grafts (vs. matched sibling; HR 2.69; p = .003), presence of grade II-IV acute graft-versus-host disease before relapse (HR 2.46; p < .001), and less than 12 months from HCT to relapse (<6 vs. > 12 months; HR 6.34; p < .001; 6-12 vs. > 12 months; HR 3.16; p = .005) were adverse prognostic factors for post-relapse survival.

Conclusion: Outcomes after alloHCT relapse remain poor regardless of the novel agent use. Innovative treatment strategies are needed to improve outcomes after relapse post-alloHCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hemonc.2020.11.006DOI Listing
December 2021

Neighborhood poverty and pediatric allogeneic hematopoietic cell transplantation outcomes: a CIBMTR analysis.

Blood 2021 01;137(4):556-568

CIBMTR, National Marrow Donor Program/Be The Match, Minneapolis, MN.

Social determinants of health, including poverty, contribute significantly to health outcomes in the United States; however, their impact on pediatric hematopoietic cell transplantation (HCT) outcomes is poorly understood. We aimed to identify the association between neighborhood poverty and HCT outcomes for pediatric allogeneic HCT recipients in the Center for International Blood and Marrow Transplant Research database. We assembled 2 pediatric cohorts undergoing first allogeneic HCT from 2006 to 2015 at age ≤18 years, including 2053 children with malignant disease and 1696 children with nonmalignant disease. Neighborhood poverty exposure was defined a priori per the US Census definition as living in a high-poverty ZIP code (≥20% of persons below 100% federal poverty level) and used as the primary predictor in all analyses. Our primary outcome was overall survival (OS), defined as the time from HCT until death resulting from any cause. Secondary outcomes included relapse and transplantation-related mortality (TRM) in malignant disease, acute and chronic graft-versus-host disease, and infection in the first 100 days post-HCT. Among children undergoing transplantation for nonmalignant disease, neighborhood poverty was not associated with any HCT outcome. Among children undergoing transplantation for malignant disease, neighborhood poverty conferred an increased risk of TRM but was not associated with inferior OS or any other transplantation outcome. Among children with malignant disease, a key secondary finding was that children with Medicaid insurance experienced inferior OS and increased TRM compared with those with private insurance. These data suggest opportunities for future investigation of the effects of household-level poverty exposure on HCT outcomes in pediatric malignant disease to inform care delivery interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2020006252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845011PMC
January 2021

Community health status and outcomes after allogeneic hematopoietic cell transplantation in the United States.

Cancer 2021 02 21;127(4):609-618. Epub 2020 Oct 21.

Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: The association of community factors and outcomes after hematopoietic cell transplantation (HCT) has not been comprehensively described. Using the County Health Rankings and Roadmaps (CHRR) and the Center for International Blood and Marrow Transplant Research (CIBMTR), this study evaluated the impact of community health status on allogeneic HCT outcomes.

Methods: This study included 18,544 adult allogeneic HCT recipients reported to the CIBMTR by 170 US centers in 2014-2016. Sociodemographic, environmental, and community indicators were derived from the CHRR, an aggregate community risk score was created, and scores were assigned to each patient (patient community risk score [PCS]) and transplant center (center community risk score [CCS]). Higher scores indicated less healthy communities. The impact of PCS and CCS on patient outcomes after allogeneic HCT was studied.

Results: The median age was 55 years (range, 18-83 years). The median PCS was -0.21 (range, -1.37 to 2.10; standard deviation [SD], 0.42), and the median CCS was -0.13 (range, -1.04 to 0.96; SD, 0.40). In multivariable analyses, a higher PCS was associated with inferior survival (hazard ratio [HR] per 1 SD increase, 1.04; 99% CI, 1.00-1.08; P = .0089). Among hematologic malignancies, a tendency toward inferior survival was observed with a higher PCS (HR, 1.04; 99% CI, 1.00-1.08; P = .0102); a higher PCS was associated with higher nonrelapse mortality (NRM; HR, 1.08; 99% CI, 1.02-1.15; P = .0004). CCS was not significantly associated with survival, relapse, or NRM.

Conclusions: Patients residing in counties with a worse community health status have inferior survival as a result of an increased risk of NRM after allogeneic HCT. There was no association between the community health status of the transplant center location and allogeneic HCT outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.33232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855526PMC
February 2021

Treatment decision-making in acute myeloid leukemia: a qualitative study of older adults and community oncologists.

Leuk Lymphoma 2021 02 11;62(2):387-398. Epub 2020 Oct 11.

Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC, USA.

Little is known about the characteristics of patients, physicians, and organizations that influence treatment decisions in older patients with AML. We conducted qualitative interviews with community oncologists and older patients with AML to elicit factors that influence their treatment decision-making. Recruitment was done purposive sampling and continued until theoretical saturation was reached, resulting in the inclusion of 15 patients and 15 oncologists. Participants' responses were analyzed using directed content analysis. Oncologists and patients considered comorbidities, functional status, emotional health, cognition, and social factors when deciding treatment; most oncologists evaluated these using clinical gestalt. Sixty-seven percent of patients perceived that treatment was their only option and that they had not been offered a choice. In conclusion, treatment decision-making is complex and influenced by patient-related factors. These factors can be assessed as part of a geriatric assessment which can help oncologists better determine fitness and guide treatment decision-making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2020.1832662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878016PMC
February 2021

Barriers to Hematopoietic Cell Transplantation for Adults in the United States: A Systematic Review with a Focus on Age.

Biol Blood Marrow Transplant 2020 12 20;26(12):2335-2345. Epub 2020 Sep 20.

James P. Wilmot Cancer Institute, Division of Hematology/Oncology, Department of Medicine, University of Rochester Medical Center, Rochester, New York. Electronic address:

Hematopoietic cell transplantation (HCT) is an effective treatment for many hematologic malignancies, and its utilization continues to rise. However, due to the difficult logistics and high cost of HCT, there are significant barriers to accessing the procedure; these barriers are likely greater for older patients. Although numerous factors may influence HCT access, no formal analysis has detailed the cumulative barriers that have been studied thus far. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to better categorize the barriers to access and referral to HCT, with a focus on the subgroup of older patients. We searched for articles published in English from PubMed, Embase, Cumulative Index for Nursing and Allied Health, and Cochrane Central Register of Controlled Trials between the database inception and January 31, 2020. We selected articles that met the following inclusion criteria: (1) study design: qualitative, cross-sectional, observational cohort, or mixed-method study designs; (2) outcomes: barriers related to patient and physician access to HCT; and (3) population: adults aged ≥18 years with hematologic malignancies within the United States. Abstracts without full text were excluded. QUALSYST methodology was used to determine article quality. Data on the barriers to access and referral for HCT were extracted, along with other study characteristics. We summarized the findings using descriptive statistics. We included 26 of 3859 studies screened for inclusion criteria. Twenty studies were retrospective cohorts and 4 were cross-sectional. There was 1 prospective cohort study and 1 mixed-method study. Only 1 study was rated as high quality, and 16 were rated as fair. Seventeen studies analyzed age as a potential barrier to HCT referral and access, with 16 finding older age to be a barrier. Other consistent barriers to HCT referral and access included nonwhite race (n = 16/20 studies), insurance status (n = 13/14 studies), comorbidities (n = 10/11 studies), and lower socioeconomic status (n = 7/8 studies). High-quality studies are lacking related to HCT barriers. Older age and nonwhite race were consistently linked to reduced access to HCT. To produce a more just health care system, strategies to overcome these barriers for vulnerable populations should be prioritized. Examples include patient and physician education, as well as geriatric assessment guided care models that can be readily incorporated into clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2020.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686105PMC
December 2020

A Personalized Prediction Model for Outcomes after Allogeneic Hematopoietic Cell Transplant in Patients with Myelodysplastic Syndromes.

Biol Blood Marrow Transplant 2020 11 8;26(11):2139-2146. Epub 2020 Aug 8.

Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.

Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potentially curative option for myelodysplastic syndromes (MDS). Mortality after HCT is high, with deaths related to relapse or transplant-related complications. Thus, identifying patients who may or may not benefit from HCT is clinically important. We identified 1514 patients with MDS enrolled in the Center for International Blood and Marrow Transplant Research Registry and had their peripheral blood samples sequenced for the presence of 129 commonly mutated genes in myeloid malignancies. A random survival forest algorithm was used to build the model, and the accuracy of the proposed model was assessed by concordance index. The median age of the entire cohort was 59 years. The most commonly mutated genes were ASXL1(20%), TP53 (19%), DNMT3A (15%), and TET2 (12%). The algorithm identified the following variables prior to HCT that impacted overall survival: age, TP53 mutations, absolute neutrophils count, cytogenetics per International Prognostic Scoring System-Revised, Karnofsky performance status, conditioning regimen, donor age, WBC count, hemoglobin, diagnosis of therapy-related MDS, peripheral blast percentage, mutations in RAS pathway, JAK2 mutation, number of mutations/sample, ZRSR2, and CUX1 mutations. Different variables impacted the risk of relapse post-transplant. The new model can provide survival probability at different time points that are specific (personalized) for a given patient based on the clinical and mutational variables that are listed above. The outcomes' probability at different time points may aid physicians and patients in their decision regarding HCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2020.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609542PMC
November 2020

Driving Distance and Patient-Reported Outcomes in Hematopoietic Cell Transplantation Survivors.

Biol Blood Marrow Transplant 2020 11 8;26(11):2132-2138. Epub 2020 Aug 8.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Long driving distances to transplantation centers may impede access to care for hematopoietic cell transplantation (HCT) survivors. As a secondary analysis from the multicenter INSPIRE study (NCT01602211), we examined baseline data from relapse-free HCT adult survivors (2 to 10 years after allogeneic or autologous HCT) to investigate the association between driving distances and patient-reported outcome (PRO) measures of distress and physical function. We analyzed predictors of elevated distress and impaired physical function using logistic regression models that operationalized driving distance first as a continuous variable and separately as a dichotomous variable (<100 versus 100+ miles). Of 1136 patients available for analysis from 6 US centers, median driving distance was 82 miles and 44% resided 100+ miles away from their HCT centers. Elevated distress was reported by 32% of patients, impaired physical function by 19%, and both by 12%. Driving distance, whether operationalized as a continuous or dichotomous variable, had no impact on distress or physical function in linear regression modeling (95% confidence interval, 1.00 to 1.00, for both PROs with driving distance as a continuous variable). In contrast, chronic graft-versus-host-disease, lower income, and lack of Internet access independently predicted both elevated distress and impaired physical function. In summary, we found no impact of driving distance on distress and physical function among HCT survivors. Our results have implications for how long-term follow-up care is delivered after HCT, with regard to the negligible impact of driving distances on PROs and also the risk of a "digital divide" worsening outcomes among HCT survivors without Internet access.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2020.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414780PMC
November 2020

The risk and prognosis of COVID-19 infection in cancer patients: A systematic review and meta-analysis.

Hematol Oncol Stem Cell Ther 2020 Jul 30. Epub 2020 Jul 30.

Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Electronic address:

Numerous studies have been published regarding outcomes of cancer patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causing the coronavirus disease 2019 (COVID-19) infection. However, most of these are single-center studies with a limited number of patients. To better assess the outcomes of this new infection in this subgroup of susceptible patients, we performed a systematic review and meta-analysis to evaluate the impact of COVID-19 infection on cancer patients. We performed a literature search using PubMed, Web of Science, and Scopus for studies that reported the risk of infection and complications of COVID-19 in cancer patients and retrieved 22 studies (1018 cancer patients). The analysis showed that the frequency of cancer among patients with confirmed COVID-19 was 2.1% (95% confidence interval [CI]: 1.3-3) in the overall cohort. These patients had a mortality of 21.1% (95% CI: 14.7-27.6), severe/critical disease rate of 45.4% (95% CI: 37.4-53.3), intensive care unit (ICU) admission rate of 14.5% (95% CI: 8.5-20.4), and mechanical ventilation rate of 11.7% (95% CI: 5.5-18). The double-arm analysis showed that cancer patients had a higher risk of mortality (odds ratio [OR] = 3.23, 95% CI: 1.71-6.13), severe/critical disease (OR = 3.91, 95% CI: 2.70-5.67), ICU admission (OR = 3.10, 95% CI: 1.85-5.17), and mechanical ventilation (OR = 4.86, 95% CI: 1.27-18.65) than non-cancer patients. Furthermore, cancer patients had significantly lower platelet levels and higher D-dimer levels, C-reactive protein levels, and prothrombin time. In conclusion, these results indicate that cancer patients are at a higher risk of COVID-19 infection-related complications. Therefore, cancer patients need diligent preventive care measures and aggressive surveillance for earlier detection of COVID-19 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hemonc.2020.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390725PMC
July 2020

Real-World Issues and Potential Solutions in Hematopoietic Cell Transplantation during the COVID-19 Pandemic: Perspectives from the Worldwide Network for Blood and Marrow Transplantation and Center for International Blood and Marrow Transplant Research Health Services and International Studies Committee.

Biol Blood Marrow Transplant 2020 12 24;26(12):2181-2189. Epub 2020 Jul 24.

Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Washington and Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

The current COVID-19 pandemic, caused by SARS-CoV-2, has impacted many facets of hematopoietic cell transplantation (HCT) in both developed and developing countries. Realizing the challenges as a result of this pandemic affecting the daily practice of the HCT centers and the recognition of the variability in practice worldwide, the Worldwide Network for Blood and Marrow Transplantation (WBMT) and the Center for International Blood and Marrow Transplant Research's (CIBMTR) Health Services and International Studies Committee have jointly produced an expert opinion statement as a general guide to deal with certain aspects of HCT, including diagnostics for SARS-CoV-2 in HCT recipient, pre- and post-HCT management, donor issues, medical tourism, and facilities management. During these crucial times, which may last for months or years, the HCT community must reorganize to proceed with transplantation activity in those patients who urgently require it, albeit with extreme caution. This shared knowledge may be of value to the HCT community in the absence of high-quality evidence-based medicine. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2020.07.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380217PMC
December 2020

Who Enrolls in an Online Cancer Survivorship Program? Reach of the INSPIRE Randomized Controlled Trial for Hematopoietic Cell Transplantation Survivors.

Biol Blood Marrow Transplant 2020 10 26;26(10):1948-1954. Epub 2020 Jun 26.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington School of Medicine, Seattle, Washington.

The internet can be a valuable tool in delivering survivorship care to hematopoietic cell transplantation (HCT) cancer survivors. We describe the reach of INSPIRE, an Internet and social media-based randomized controlled trial, to address healthcare and psychosocial needs of HCT survivors. All survivors 2-10 years after HCT for hematologic malignancy or myelodysplasia from 6 transplantation centers in the US were approached by mail and follow-up calls. Eligible participants had access to the Internet, an email address, and did not have active disease in the past 2 years. We used logistic regression to determine characteristics of eligible survivors who were more or less likely to enroll. Of 2578 eligible HCT survivors, 1065 (41%) enrolled in the study. The mean age of enrollees was 56.3 ± 12.6 years (range, 19 to 89 years), 52% were male, and 94% were white. Survivors less likely to enroll included those who were male, age <40 years, and who received an autologous transplant (all P < .001). Compared with white survivors, African Americans were less likely to enroll (P < .001), whereas Native Americans/Alaska Natives were more likely to join the study (P = .03). The reach of the INSPIRE program was broad, including to survivors who traditionally have less access to resources, such as Native Americans/Alaskan Natives and rural residents. Strategies are still needed to improve the enrollment of online studies of survivorship resources for males, young adults, African American, and autologous HCT survivors because their use may improve outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2020.06.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529848PMC
October 2020

Quality-of-Life Trajectories in Adolescent and Young Adult versus Older Adult Allogeneic Hematopoietic Cell Transplantation Recipients.

Biol Blood Marrow Transplant 2020 08 19;26(8):1505-1510. Epub 2020 May 19.

Department of Pediatric Hematology Oncology and Bone Marrow Transplant, Cleveland Clinic Foundation, Cleveland, Ohio. Electronic address:

Hematopoietic cell transplantation (HCT) is physically and psychologically challenging, potentially exposing patients to quality-of-life (QoL) impairments. Adolescent and young adults (AYAs, aged 15 to 39 years) are a vulnerable cohort facing multiple hurdles due to dynamic changes in several aspects of their lives. The AYA population may be particularly prone to QoL issues during HCT. We hypothesized that due to the unique psychosocial challenges faced by AYAs, they would have an inferior quality of life. We studied QoL differences between AYA (aged 15 to 39 years) and older adult (aged 40 to 60 years) allogeneic HCT recipients before and after HCT. Additionally, we determined if pre-HCT QoL for AYA transplant recipients changed over time. QoL data were collected prospectively before and after transplant on 431 recipients aged 15 to 60 years from June 2003 through December 2017 using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) questionnaire. Repeated-measures analysis of variance was used to assess differences among age groups. Pearson correlation (r) was used to determine if baseline QoL had improved after HCT from June 2003 through December 2017 in the AYA cohort. QoL did not differ among younger AYAs, older AYAs, or older adults at any time in the first year after allogeneic HCT. At 1 year post-HCT, total FACT-BMT score and all FACT-BMT domains except physical well-being improved from pre-HCT in all age groups. From 2003 to 2017, AYA allogeneic recipients experienced modest improvement in additional concerns (r = 0.26, P = .003), trial outcome index (r = 0.23, P = .008), and total FACT-BMT score (r = 0.19, P = .031), although no improvements were seen in physical, social, emotional, or functional well-being. Contrary to our hypothesis, we found that QoL in the AYA population is similar to that of older adults before and after HCT. Improvements in QoL of AYA allogeneic patients since 2003 were driven by the additional concerns domain, which addresses multiple psychosocial aspects such as vocation, hobbies, and acceptance of illness. Continued efforts to tailor treatment and support for AYA HCT recipients is critical to improving QoL outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2020.03.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371542PMC
August 2020

Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide.

Biol Blood Marrow Transplant 2020 08 17;26(8):1459-1468. Epub 2020 May 17.

(7)Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, Florida.

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2020.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391266PMC
August 2020

Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT.

J Clin Oncol 2020 06 4;38(18):2062-2076. Epub 2020 May 4.

Division of Clinical Hematology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.

Purpose: There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor.

Methods: We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, < .0071 in multivariable analysis and < .00025 in direct pairwise comparisons were considered statistically significant.

Results: In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group.

Conclusion: Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.19.00396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302955PMC
June 2020

Return-to-Work Guidelines and Programs for Post-Hematopoietic Cell Transplantation Survivors: An Initial Survey.

Biol Blood Marrow Transplant 2020 08 29;26(8):1520-1526. Epub 2020 Apr 29.

Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington School of Medicine, Seattle, Washington.

Hematopoietic cell transplantation (HCT) requires absence from work, with potential consequences of unemployment and early retirement. Risk factors for failure to return to work (RTW) following HCT have been reported, but there is little information about how transplant centers facilitate the RTW transition for their post-HCT patients. In the present study, we aimed to determine (1) whether transplant centers have guidelines for RTW post-HCT and the consistency of these guidelines and (2) whether centers have RTW programs for their patients, and the characteristics of these programs. We surveyed representatives from 150 adult transplant centers regarding their RTW guidelines and RTW programs. Centers were selected if they performed at least 50 HCTs (autologous [auto] and/or allogeneic [allo]) annually. The online survey contained 32 open-ended and closed-ended questions and 3 questions each eliciting respondents' demographic and transplant centers information. We received completed surveys from 45 centers (30% response rate). Forty-four percent of centers reported having RTW guidelines. All centers recommend RTW at 6 months or less after HCT for their auto-HCT recipients; recommendations for allo-HCT recipients ranged from 4 months to >1 year after HCT having jobs involving interactions with children, sick people, and animals was considered a reason to delay RTW by most centers. Although 87% of centers endorsed that RTW is a problem for post-HCT recipients, only 36% reported having an RTW program for their patients. The majority validated that RTW programs would be either somewhat helpful (36%) or very helpful (51%) for their patients. The majority of responding HCT centers believe that RTW is a problem for patients after HCT; however, consistent guidelines and RTW programs are lacking. With increasing numbers of HCT survivors, efforts to create standardized guidelines and to develop RTW programs are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2020.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546432PMC
August 2020

To D or not to D: vitamin D in hematopoietic cell transplantation.

Bone Marrow Transplant 2020 11 25;55(11):2060-2070. Epub 2020 Apr 25.

Blood and Marrow Transplant Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

Vitamin D plays an essential role in bone health, immune tolerance, and immune modulation. Autologous and allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk of vitamin D deficiency, which may increase risks of bone loss and fracture, graft-versus-host disease (GVHD), and relapse, and can delay hematologic and immune recovery following HCT. Growing evidence indicates that vitamin D may have a role as an immunomodulator, and supplementation during HCT may decrease the risk of GVHD, infection, relapse, and mortality. In this paper, we review the role of vitamin D and its association with HCT outcomes and discuss prevention and treatment of vitamin D deficiency after HCT in adult recipients. We review the role of monitoring of vitamin D levels pre- and post-HCT and its supplementation in appropriate patients. We also review the use of bone densitometry prior to HCT and in long-term follow-up and the treatment of osteoporosis in this high-risk population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-020-0904-7DOI Listing
November 2020
-->