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Transplant Cell Ther ; 27(5): 438.e1-438.e6, 2021 05.
Article in English | MEDLINE | ID: covidwho-1083120


An evidence-based triage plan for cellular therapy distribution is critical in the face of emerging constraints on healthcare resources. We evaluated the impact of treatment delays related to COVID-19 on patients scheduled to undergo hematopoietic cell transplantation (HCT) or chimeric antigen receptor T-cell (CAR-T) therapy at our center. Data were collected in real time between March 19 and May 11, 2020, for patients who were delayed to cellular therapy. We evaluated the proportion of delayed patients who ultimately received cellular therapy, reasons for not proceeding to cellular therapy, and changes in disease and health status during delay. A total of 85 patients were delayed, including 42 patients planned for autologous HCT, 36 patients planned for allogeneic HCT, and 7 patients planned for CAR-T therapy. Fifty-six of these patients (66%) since received planned therapy. Five patients died during the delay. The most common reason for not proceeding to autologous HCT was good disease control in patients with plasma cell dyscrasias (75%). The most common reason for not proceeding to allogeneic HCT was progression of disease (42%). All patients with acute leukemia who progressed had measurable residual disease (MRD) at the time of delay, whereas no patient without MRD at the time of delay progressed. Six patients (86%) ultimately received CAR-T therapy, including 3 patients who progressed during the delay. For patients with high-risk disease such as acute leukemia, and particularly those with MRD at the time of planned HCT, treatment delay can result in devastating outcomes and should be avoided if at all possible.

COVID-19 , Hematopoietic Stem Cell Transplantation , Immunotherapy, Adoptive , Pandemics , SARS-CoV-2 , Time-to-Treatment , Adult , Aged , Allografts , Amyloidosis/therapy , Anemia, Aplastic/therapy , COVID-19/complications , COVID-19/epidemiology , COVID-19/transmission , Civil Defense , Cross Infection/epidemiology , Cross Infection/prevention & control , Disease Progression , Evidence-Based Practice/organization & administration , Female , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Humans , Infection Control/methods , Infectious Disease Transmission, Professional-to-Patient , Leukemia/mortality , Leukemia/pathology , Leukemia/therapy , Male , Middle Aged , Myelodysplastic-Myeloproliferative Diseases/mortality , Myelodysplastic-Myeloproliferative Diseases/therapy , Neoplasm, Residual , Neoplasms/mortality , Neoplasms/therapy , New York City/epidemiology , Resource Allocation , Time-to-Treatment/statistics & numerical data , Transplantation, Autologous , Triage/organization & administration , Young Adult
Br J Haematol ; 191(2): 194-206, 2020 10.
Article in English | MEDLINE | ID: covidwho-966626


Haematology patients receiving chemo- or immunotherapy are considered to be at greater risk of COVID-19-related morbidity and mortality. We aimed to identify risk factors for COVID-19 severity and assess outcomes in patients where COVID-19 complicated the treatment of their haematological disorder. A retrospective cohort study was conducted in 55 patients with haematological disorders and COVID-19, including 52 with malignancy, two with bone marrow failure and one immune-mediated thrombotic thrombocytopenic purpura (TTP). COVID-19 diagnosis coincided with a new diagnosis of a haematological malignancy in four patients. Among patients, 82% were on systemic anti-cancer therapy (SACT) at the time of COVID-19 diagnosis. Of hospitalised patients, 37% (19/51) died while all four outpatients recovered. Risk factors for severe disease or mortality were similar to those in other published cohorts. Raised C-reactive protein at diagnosis predicted an aggressive clinical course. The majority of patients recovered from COVID-19, despite receiving recent SACT. This suggests that SACT, where urgent, should be administered despite intercurrent COVID-19 infection, which should be managed according to standard pathways. Delay or modification of therapy should be considered on an individual basis. Long-term follow-up studies in larger patient cohorts are required to assess the efficacy of treatment strategies employed during the pandemic.

Antineoplastic Agents/therapeutic use , COVID-19/complications , Hematologic Diseases/complications , Immunotherapy , Adult , Age Factors , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Blacks , COVID-19/mortality , COVID-19/therapy , Comorbidity , Cross Infection/complications , Female , Hematologic Diseases/drug therapy , Hematologic Diseases/mortality , Hematologic Diseases/therapy , Hematopoietic Stem Cell Transplantation , Humans , Leukemia/complications , Leukemia/drug therapy , Leukemia/mortality , London/epidemiology , Lymphoma/complications , Lymphoma/drug therapy , Lymphoma/mortality , Male , Middle Aged , Respiration, Artificial , Retrospective Studies , Risk Factors , SARS-CoV-2 , Thrombophilia/drug therapy , Thrombophilia/etiology , Treatment Outcome , Young Adult
Biol Blood Marrow Transplant ; 26(7): 1312-1317, 2020 07.
Article in English | MEDLINE | ID: covidwho-208523


The COVID-19 pandemic has created significant barriers to timely donor evaluation, cell collection, and graft transport for allogeneic hematopoietic stem cell transplantation (allo-HCT). To ensure availability of donor cells on the scheduled date of infusion, many sites now collect cryopreserved grafts before the start of pretransplantation conditioning. Post-transplantation cyclophosphamide (ptCY) is an increasingly used approach for graft-versus-host disease (GVHD) prophylaxis, but the impact of graft cryopreservation on the outcomes of allo-HCT using ptCY is not known. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared the outcomes of HCT using cryopreserved versus fresh grafts in patients undergoing HCT for hematologic malignancy with ptCY. We analyzed 274 patients with hematologic malignancy undergoing allo-HCT between 2013 and 2018 with cryopreserved grafts and ptCY. Eighteen patients received bone marrow grafts and 256 received peripheral blood stem cell grafts. These patients were matched for age, graft type, disease risk index (DRI), and propensity score with 1080 patients who underwent allo-HCT with fresh grafts. The propensity score, which is an assessment of the likelihood of receiving a fresh graft versus a cryopreserved graft, was calculated using logistic regression to account for the following: disease histology, Karnofsky Performance Score (KPS), HCT Comorbidity Index, conditioning regimen intensity, donor type, and recipient race. The primary endpoint was overall survival (OS). Secondary endpoints included acute and chronic graft-versus-host disease (GVHD), non-relapse mortality (NRM), relapse/progression and disease-free survival (DFS). Because of multiple comparisons, only P values <.01 were considered statistically significant. The 2 cohorts (cryopreserved and fresh) were similar in terms of patient age, KPS, diagnosis, DRI, HCT-CI, donor/graft source, and conditioning intensity. One-year probabilities of OS were 71.1% (95% confidence interval [CI], 68.3% to 73.8%) with fresh grafts and 70.3% (95% CI, 64.6% to 75.7%) with cryopreserved grafts (P = .81). Corresponding probabilities of OS at 2 years were 60.6% (95% CI, 57.3% to 63.8%) and 58.7% (95% CI, 51.9% to 65.4%) (P = .62). In matched-pair regression analysis, graft cryopreservation was not associated with a significantly higher risk of mortality (hazard ratio [HR] for cryopreserved versus fresh, 1.05; 95% CI, .86 to 1.29; P = .60). Similarly, rates of neutrophil recovery (HR, .91; 95% CI, .80 to 1.02; P = .12), platelet recovery (HR, .88; 95% CI, .78 to 1.00; P = .05), grade III-IV acute GVHD (HR, .78; 95% CI, .50 to 1.22; P = .27), NRM (HR, 1.16; 95% CI, .86 to 1.55; P = .32) and relapse/progression (HR, 1.21; 95% CI, .97 to 1.50; P = .09) were similar with cryopreserved grafts versus fresh grafts. There were somewhat lower rates of chronic GVHD (HR, 78; 95% CI, .61 to .99; P = .04) and DFS (HR for treatment failure, 1.19; 95% CI, 1.01 to 1.29; P = .04) with graft cryopreservation that were of marginal statistical significance after adjusting for multiple comparisons. Overall, our data indicate that graft cryopreservation does not significantly delay hematopoietic recovery, increase the risk of acute GVHD or NRM, or decrease OS after allo-HCT using ptCY.

Bone Marrow Transplantation/methods , Coronavirus Infections/epidemiology , Cryopreservation/methods , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/methods , Leukemia/therapy , Lymphoma/therapy , Myelodysplastic Syndromes/therapy , Pneumonia, Viral/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19 , Cohort Studies , Cyclophosphamide/therapeutic use , Female , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Graft vs Host Disease/pathology , Histocompatibility Testing , Humans , Leukemia/immunology , Leukemia/mortality , Leukemia/pathology , Lymphoma/immunology , Lymphoma/mortality , Lymphoma/pathology , Male , Middle Aged , Myelodysplastic Syndromes/immunology , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/pathology , Pandemics , Siblings , Survival Analysis , Transplantation Conditioning/methods , Transplantation, Homologous , United States/epidemiology , Unrelated Donors/supply & distribution