Human chronic myelogenous leukaemia is characterized by a reciprocal translocation between chromosomes 9 and 22 resulting in an abbreviated form of chromosome 22 and the transfer of the abl cellular oncogene from chromosome 9 into the bcr gene of chromosome 22. Characterization of an 8-kilobase RNA specific to chronic myelogenous leukaemia shows it to be a fused transcript of the two genes. The fused protein that would be produced is probably involved in the malignant process.

depend on a specific early diagnosis. Since 1994, we have come a long way in understanding the role of proinflammatory cytokines at the cellular level both within the fetus and in a possible relationship to fetal brain damage. Heretofore, birth markers such as Apgar scores, electronic fetal monitoring, neuroimaging, and onset of seizures in the first 48 hours are not specific and not sensitive. In the 1994 editorial, I stated that more accurate markers of hypoxia were needed and should develop as our understanding of the biochemical mechanisms unfold. Now that the biochemical mechanisms are unfolding, and once we can get specific levels of cytokines in the blood and the cerebrospinal fluid, interventions can be tried under randomized and controlled conditions with the hope of preventing some of the devastating consequences of hypoxic-ischemic brain damage.-RCC) ABSTRACTAt present, an estimated 1 in 5 leukemic patients receives a bone marrow or stem cell transplant from an unrelated donor or an HLA-mismatched related donor. Cord blood grafts from unrelated donors have been successful, most often in children. Hematopoiesis recovers more slowly than with bone marrow grafts, contributing to relatively high rates of infection and early death. This study examined outcomes in adults with leukemia, from 16 to 60 years of age, who received transplants of hematopoietic stem cells from unrelated donors. Data were acquired from the International Bone Marrow Transplant Registry and from the National Cord Blood Program of the New York Blood Center. Cord blood was mismatched for 1 HLA antigen in 34 cases and for 2 antigens in 116 others. Bone marrow had 1 HLA mismatch in 83 cases, whereas 367 patients received HLA-matched bone marrow. The patients given cord blood were younger than those given marrow transplants and likelier to have advanced leukemia.Median follow-up intervals were 4 years for marrow recipients and 40 months for those given cord blood transplants. For patients whose neutrophils and platelets recovered, recovery times were shorter after marrow transplantation and longest (27 days) after cord blood transplantation. A similar pattern was found for platelet recovery, with a median recovery interval of 60 days after cord blood transplantation. There were no major differences in recovery of either neutrophils or platelets after 12 months. Acute graft-versus-host disease (GVHD) was less likely after transplanting mismatched cord blood than mismatched bone marrow. Among patients who lived 3 months or longer, chronic GVHD was most frequent in patients given cord blood. The fewest treatment-related deaths were in patients given HLAEthics, Medicolegal Issues, and Public Policy 295

Infection with SARS-CoV-2, the cause of coronavirus infectious disease-19 , has caused a pandemic with >850,000 cases worldwide and increasing. Several studies report outcomes of COVID-19 in predominately well persons. There are also some data on COVID-19 in persons with predominately solid cancer but controversy whether these persons have the same outcomes. We conducted a cohort study at two centres in Wuhan, China, of 128 hospitalised subjects with haematological cancers, 13 (10%) of whom developed COVID-19. We also studied 226 health care providers, 16 of whom developed COVID-19 and 11 of whom were hospitalised. Co-variates were compared with the 115 subjects with haematological cancers without COVID-19 and with 11 hospitalised health care providers with COVID-19. There were no significant differences in baseline co-variates between subjects with haematological cancers developing or not developing COVID-19. Case rates for COVID-19 in hospitalised subjects with haematological cancers was 10% (95% Confidence Interval [CI], 6, 17%) compared with 7% (4, 12%; P = 0.322) in health care providers. However, the 13 subjects with haematological cancers had more severe COVID-19 and more deaths compared with hospitalised health care providers with COVID-19. Case fatality rates were 62% (32, 85%) and 0 (0, 32%; P = 0.002). Hospitalised persons with haematological cancers have a similar case rate of COVID-19 compared with normal health care providers but have more severe disease and a higher case fatality rate. Because we were unable to identify specific risk factors for COVID-19 in hospitalised persons with haematological cancers, we suggest increased surveillance and possible protective isolation.

Chronic graft-versus-host disease (cGVHD) is the leading cause of late treatmentrelated deaths among recipients of allogeneic bone marrow and blood transplants. However, cGVHD is also associated with fewer relapses. We sought to determine whether severity of cGVHD predicts the magnitude of these effects. One impediment to such an analysis is the current limited/extensive grading system for cGVHD because this classification was designed to identify patients likely to benefit from systemic immune suppression and does not capture the severity of multiorgan involvement. We, therefore, first developed a grading system predictive for survival by using data from 1827 HLAmatched sibling allotransplant recipients reported to the International Bone Marrow Transplant Registry (IBMTR). We found Karnofsky performance score, diarrhea, weight loss, and cutaneous and oral involvement to be independent prognostic variables, from which we generated a grading scheme. We tested this scheme, the limited/extensive classification sys-

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Bone marrow transplantation (BMT) can cure myelodysplastic syndrome (MDS), although transplantation carries significant risks of morbidity and mortality. Because the optimal timing of HLA-matched BMT for MDS is unknown, we constructed a Markov model to examine 3 transplantation strategies for newly diagnosed MDS: transplantation at diagnosis, transplantation at leukemic progression, and transplantation at an interval from diagnosis but prior to leukemic progression. Analyses using individual patient risk-assessment data from transplantation and non-

PURPOSE Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR). PATIENTS AND METHODS We reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS). RESULTS Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and > or = 65 years had 2-year survival rates as follows: 44% (95% CI, 37% to 52%), 50% (95% CI, 41% to 59%), 34% (95% CI, 25% to 43%), and 36% (95% CI, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% CI, 35% to 49%), 35% (95% CI, 27% to 43%), 45% (95% CI, 36% to 54%), and 38% (95% CI, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P > .3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS. CONCLUSION With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.

Data on 405 patients with chronic myelogenous leukemia who received bone marrow transplants in chronic phase were analyzed for factors predictive of outcome. The 4-year actuarial probability of relapse was 19% (95% confidence interval [CI], 12% to 28%) and of survival, 55%. In multivariate analyses the probability of relapse was higher for recipients of T-cell-depleted bone marrow compared with recipients of non-T-cell-depleted bone marrow (relative risk, 5.4; P less than 0.0001) and for patients who did not develop chronic graft-versus-host disease (95% CI, 50% to 60%) with patients who did (relative risk, 3.1; P less than 0.01). The probability of survival was lower for patients who developed moderate to severe acute graft-versus-host disease than for patients with no or mild acute graft-versus-host disease (relative risk, 3.7; P less than 0.0001), and in patients aged 20 or older than in younger patients (relative risk, 2.6; P less than 0.0002). Duration of disease before transplant was not associated with outcome. Bone marrow transplantation done in the chronic phase of chronic myelogenous leukemia offers some patients prolonged leukemia-free survival. The T-cell-depleted grafts are associated with an increased probability of relapse.