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BACKGROUND AND OBJECTIVES: Graft failure (GF) after cord blood transplant (CBT) has decreased with improved supportive care and cord selection strategies. We aimed to evaluate cord blood selection and factors associated with retransplantation on the incidence of GF, determine risk factors for GF including host antibodies to Kell antigen and evaluate survival after GF. MATERIALS AND METHODS: We retrospectively reviewed 84 patients who underwent CBT at the University of Oklahoma between 2000 and 2016 and compared outcomes in patients with/without engraftment by Day 28. The nonengraftment cohort was further divided into patients who underwent retransplantation. Kaplan-Meier curves with log-rank tests were calculated to assess the association between mortality and engraftment. RESULTS: Engraftment following CBT was high at 81%, with 52% engrafting by Day 28 and an additional 29% engrafting by a median of 36 days. Retransplantation led to 88% engraftment at a median of 53 days. Overall, 75% of the 40 patients who did not engraft by Day 28 died. Female sex and total nucleated cell count < 3.5/kg were significantly associated with lack of engraftment and higher mortality. Antibodies to Kell fetal antigen were not identified. Retransplantation by Day 28 for primary GF conferred a survival advantage. CONCLUSION: This study demonstrates that failure to engraft by 28 days was associated with increased mortality, and risk was mitigated with early retransplantation. Female sex and low total cell dose were associated with increased mortality. Early identification of GF coupled with early retransplantation can reduce mortality in CBT.

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The COVID-19 pandemic has led to significant global health and economic consequences. There is an unmet need to define a molecular fingerprint of severity of the disease that may guide an early, rational and directed intervention preventing severe illness. We collected plasma from patients with moderate (nine cases), severe (22 cases) and critical (five cases) COVID-19 within three days of hospitalization (approximately one week after symptom onset) and used a cytokine antibody array to screen the 105 cytokines included in the array. We found that I-TAC, IP-10, ST2 and IL-1ra were significantly upregulated in patients with critical disease as compared to the non-critical (moderate and severe combined). ELISA further quantified I-TAC levels as 590.24±410.89, 645.35±517.59 and 1613.53±1010.59 pg/ml in moderate, severe and critical groups, respectively. Statistical analysis showed that I-TAC levels were significantly higher in patients with critical disease when compared with moderate (p = 0.04), severe (p = 0.03) or the combined non-critical (p = 0.02) group. Although limited by the low sample numbers, this study may suggest a role of I-TAC as a potential early marker to discriminate between critical and non-critical COVID-19 cases. Such knowledge is urgently needed for appropriate allocation of resources and to serve as a platform for future research towards early interventions that could mitigate disease severity and save lives.

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Understanding the subclinical pathway to cellular engraftment following haemopoietic stem cell transplantation (HSCT) has historically been limited by infrequent marrow biopsies, which increase the risk of infections and might poorly represent the health of the marrow space. Nuclear imaging could represent an opportunity to evaluate the entire medullary space non-invasively, yielding information about cell number, proliferation, or metabolism. Because imaging is not associated with infectious risk, it permits assessment of neutropenic timepoints that were previously inaccessible. This Viewpoint summarises the data regarding the use of nuclear medicine techniques to assess the phases of HSCT: pre-transplant homoeostasis, induced aplasia, early settling and engraftment of infused cells, and later recovery of lymphocytes that target cancers or mediate tolerance. Although these data are newly emerging and preliminary, nuclear medicine imaging approaches might advance our understanding of HSCT events and lead to novel recommendations to enhance outcomes.

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BACKGROUND: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n = 916), non-Hodgkin lymphoma (NHL; n = 3546) and plasma cell myeloma (PCM; n = 4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS. RESULTS: 335 MDS/AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR = 4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR = 2.5 [1.1, 2.5]); (2) ≥3 versus 1 line of chemotherapy for NHL (HR = 1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR = 2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort. CONCLUSIONS: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.

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Clinical assessment of bone marrow is limited by an inability to evaluate the marrow space comprehensively and dynamically and there is no current method for automatically assessing hematopoietic activity within the medullary space. Evaluating the hematopoietic space in its entirety could be applicable in blood disorders, malignancies, infections, and medication toxicity. In this paper, we introduce a CT/PET 3D automatic framework for measurement of the hematopoietic compartment proliferation within osseous sites. We first perform a full-body bone structure segmentation using 3D graph-cut on the CT volume. The vertebrae are segmented by detecting the discs between adjacent vertebrae. Finally, we register the bone marrow CT volume with its corresponding PET volume and capture the spinal bone marrow volume. The proposed framework was tested on 17 patients, achieving an average accuracy of 86.37% and a worst case accuracy of 82.3% in automatically extracting the aggregate volume of the spinal marrow cavities.