Ioannis Politikos's research while affiliated with Memorial Sloan Kettering Cancer Center and other places

... Futile searches, defined as those that will not yield a guaranteed URD of the minimal acceptable attributes in the time required for appropriate clinical care, should be abandoned. Utilization of all alternative donors (ie, 5-7/8 URD, 3,38 haploidentical, 39 and cord blood [40][41][42][43][44][45] ) is needed to facilitate donors for all in the time required for optimized transplantation. These efforts as well as addressing the intersectional impacts of patient socioeconomic status, 16 including insurance coverage, 46 language barriers, 47 and health literacy, will be critical to address structural barriers to care 48 and advance equity for allograft candidates across populations. ...

... Unrelated donor (URD) transplants are the most common alternative, 1 and their use is increasing with the advent of posttransplant cyclophosphamide or abataceptbased graft-versus-host disease prophylaxis. [2][3][4] This trend may be enhanced by the emerging data that could support the use of younger 8/8 URDs over older sibling donors, 5 the recognition of the limitations associated with older haploidentical donors 6,7 or those against whom the patient has donor-specific HLA antibodies, [8][9][10] and the decline in cord blood transplant activity. 1 For these reasons, prompt URD availability is critically important, especially as acute leukemia and other aggressive myeloid malignancies are the most common transplant indications. 1 Traditionally, the priority in URD selection has been optimizing the HLA match. More recently, the advantage of using a younger URD (ie, age ≤35 years) has been demonstrated. ...

... Futile searches, defined as those that will not yield a guaranteed URD of the minimal acceptable attributes in the time required for appropriate clinical care, should be abandoned. Utilization of all alternative donors (ie, 5-7/8 URD, 3,38 haploidentical, 39 and cord blood [40][41][42][43][44][45] ) is needed to facilitate donors for all in the time required for optimized transplantation. These efforts as well as addressing the intersectional impacts of patient socioeconomic status, 16 including insurance coverage, 46 language barriers, 47 and health literacy, will be critical to address structural barriers to care 48 and advance equity for allograft candidates across populations. ...

... 39 The outcomes vary by variant, and are worse in those patients with lymphopenia, higher ferritin and who develop COVID-19 close to infusion. 38,40,41 Therapies such as remdesivir, nirmatrelvir/ritonavir and immunizations have contributed to improved outcomes in recent years. 42,43 Although the World Health Organization (WHO) declared that the pandemic no longer constitutes a 'public health emergency of international concern' on May 5, 2023, COVID-19 is still present in localized small outbreaks and is still considered to be a risk for morbidity and mortality in CAR-T recipients. ...

... Our current practice is to offer allo-HCT to patients with TP53-mutated MDS/AML least likely to suffer transplantation-related morbidity and mortality. We select these patients on the basis of very good performance status (KPS > 90) and minimal comorbidities [48,66,67] (Table 3). In patients not meeting these strict characteristics, we are unlikely to offer allo-HCT to patients with biallelic alterations and/or adverse risk cytogenetics. ...

... The latter question has recently been addressed by DeWolf et al. in a systematic study of TCR repertoires across multiple different tissue sites. 71 The authors identified anatomically defined TCR repertoires and motifs that only partially overlapped with circulating TCR repertoires, underscoring the importance of the study of tissue-resident memory T cells. Besides providing a deeper understanding of T cells, scRNA-seq studies of tissue biopsies should also investigate the role of other cell types in the pathogenesis of GvHD, such as B cells, for which Poe et al. have provided a baseline by defining their transcriptional profiles in peripheral blood and bone marrow. ...

... In this issue of the JCI, Prockop et al. (12) present the combined clinical results of three separate phase I or II clinical trials that treated a total of 67 subjects with refractory CMV viremia or organ disease with the adoptive transfer of banked, third-party CMV pp65-sensitized virus-specific T cells (CMVpp65-VSTs). In contrast with donor-derived patient-specific VSTs, each third-party CMVpp65-VST line selected for infusion was (a) restricted by an HLA allele that was shared by the patient and the patient's HCT donor and (b) shared at least two HLA alleles with the patient (Figure 1). ...

... Centers should also determine the prioritization of haploidentical donors relative to URDs and whether cord blood grafts will be considered if no adult donor can be secured in the time required for appropriate care, especially given use of cord blood greatly speeds transplantation as we have previously reported. 15 Moreover, centers are ethically obliged to inform patients whether timely URD procurement is unlikely, 11,30,31 especially because these patients are commonly from underserved racial/ethnic groups. The futility of pursuing a matched donor and the potential need for alternative donors should also be explained. ...

... Nevertheless, in this population rate of respiratory failure and COVID-related mortality is lower in the Omicron versus the pre-Omicron period (7.8% versus 36.8%) [13,14]. Age, fewer vaccine doses, and diagnosis of acute myeloid leukemia or myelodysplastic syndrome are considered independent predictors of progression to severe COVID-19 or death in HM patients during the Omicron period [13]. ...

... Centers should also determine the prioritization of haploidentical donors relative to URDs and whether cord blood grafts will be considered if no adult donor can be secured in the time required for appropriate care, especially given use of cord blood greatly speeds transplantation as we have previously reported. 15 Moreover, centers are ethically obliged to inform patients whether timely URD procurement is unlikely, 11,30,31 especially because these patients are commonly from underserved racial/ethnic groups. The futility of pursuing a matched donor and the potential need for alternative donors should also be explained. ...