Relapse remains the most common cause of treatment failure for patients with acute myeloid leukemia (AML) who undergo allogeneic stem cell transplantation (alloSCT), and carries a grave prognosis. Multiple studies have identified the presence of measurable residual disease (MRD) assessed by flow cytometry before alloSCT as a strong predictor of relapse, but it is not clear how these findings apply to patients who test positive in molecular MRD assays, which have far greater sensitivity. We analyzed pretransplant blood and bone marrow samples by reverse-transcription polymerase chain reaction in 107 patients with NPM1-mutant AML enrolled in the UK National Cancer Research Institute AML17 study. After a median follow-up of 4.9 years, patients with negative, low (<200 copies per 105ABL in the peripheral blood and <1000 copies in the bone marrow aspirate), and high levels of MRD had an estimated 2-year overall survival (2y-OS) of 83%, 63%, and 13%, respectively (P < .0001). Focusing on patients with low-level MRD before alloSCT, those with FLT3 internal tandem duplications(ITDs) had significantly poorer outcome (hazard ratio [HR], 6.14; P = .01). Combining these variables was highly prognostic, dividing patients into 2 groups with 2y-OS of 17% and 82% (HR, 13.2; P < .0001). T-depletion was associated with significantly reduced survival both in the entire cohort (2y-OS, 56% vs 96%; HR, 3.24; P = .0005) and in MRD-positive patients (2y-OS, 34% vs 100%; HR, 3.78; P = .003), but there was no significant effect of either conditioning regimen or donor source on outcome. Registered at ISRCTN (http://www.isrctn.com/ISRCTN55675535).

Coronavirus disease 2019 (COVID-19) is caused by the novel SARS-CoV-2 virus and has been declared a pandemic on the 9th of March by the WHO. A hallmark of COVID-19 management is supportive care and there is still no convincing evidence for a treatment which will reduce mortality. Severe COVID-19-associated sepsis characterized by acute respiratory distress syndrome (ARDS), secondary bacterial pneumonias, thrombotic complications, myocarditis, and gastrointestinal involvement are more prevalent in those with comorbidities such as hypertension, diabetes, cardiac disease, cancer and age >70 years. 1,2 There is a paucity of data on COVID-19's impact on bone marrow transplant patients. Herein we reflect on the course of seven bone marrow transplant recipients in Birmingham Heartlands Hospital who have been found positive for SARS-CoV-2 RNA on real time polymerase chain reaction (RT-PCR) from nasopharyngeal swabs done in the context of symptoms (fever, cough, dyspnoea, and fatigue) or inpatient contact. The median age was 61 years (range 40-74). Out of these, five (71%) were female and two (29%) were male. The median time from stem cell infusion to the diagnosis of SARS-CoV-2 virus was 61 days (range 7-343). Patients were screened for SARS-CoV-2 via an RT-PCR-based technique.

BackgroundReduced intensity conditioning regimens permit the delivery of a potentially curative graft-versus-leukemia effect in older patients with acute myeloid leukemia. Although T-cell depletion is increasingly used to reduce the risk of graft-versus-host disease its impact on the graft-versusleukemia effect and long-term outcome post-transplant is unknown. Design and MethodsWe have characterized pre-and post-transplant factors determining overall survival in 168 patients with acute myeloid leukemia transplanted using an alemtuzumab based reduced intensity conditioning regimen with a median duration of follow-up of 37 months. ResultsThe 3-year overall survival for patients transplanted in CR1 or CR2/CR3 was 50% (95% CI, 38% to 62%) and 44% (95% CI, 31% to 56%), respectively compared to 15% (95% CI, 2% to 36%) for patients with relapsed/refractory disease. Multivariate analysis demonstrated that both survival and disease relapse were influenced by status at transplant (P=0.008) and presentation cytogenetics (P=0.01). Increased exposure to cyclosporine A (CsA) in the first 21 days post-transplant was associated with an increased relapse risk (P<0.0001) and decreased overall survival (P<0.0001). ConclusionsDisease stage, presentation karyotype and post-transplant CsA exposure are important predictors of outcome in patients undergoing a T-cell depleted reduced intensity conditioning allograft for acute myeloid leukemia. These data confirm the presence of a potent graft-versusleukemia effect after a T-cell depleted reduced intensity conditioning allograft in acute myeloid leukemia and identify CsA exposure as a manipulable determinant of outcome in this setting.Key words: reduced intensity conditioning, graft-versus-leukemia, acute myeloid leukemia. leukemia. Haematologica 2010;95:989-995. doi:10.3324/haematol.2009 This is an open-access paper. Citation: Craddock C, Nagra S, Peniket A, Brookes C, Buckley L, Nikolousis E, Duncan N, Tauro S, Yin J, Liakopoulou E, Kottaridis P, Snowden J, Milligan D, Cook G, Tholouli E, Littlewood T, Peggs K, Vyas P, Clark F, Cook M, MacKinnon S, and Russell N. Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid leukemia

myelodysplasia, 7 T cell non Hodgkin's lymphoma 6 aplastic leukaemia and 7 myelofibrosis At transplantation 40% (N=133) patients had normal and 60%(N=198) high BMI with 14% of patients being obese (BMI>30). After a median follow-up of 24 months (range:2-79), the mean overall survival(OS) in patients undergoing allograft with normal BMI was 31 months as compared to 39 with high BMI ( p:0.06). The mean progression free survival(PFS) in patients undergoing allograft with normal BMI was 33 months as compared to 38 with high BMI (p:0.13).16% of the patients in the high and obese BMI group developed acute GvHD with 8% grade III-IV and 28% in the normal BMI group with 14% grade III-IV acute GvHD.(p.0.11).17% of the patients in the high BMI group developed chronic GvHD and 30% of the patients in the normal BMI group (p:0.09).However higher infection rates and more days of inpatient stay in the first year post transplant were observed in the high BMI and obese patients but there was no difference in ITU admissions. This study shows that high BMI and obesity does not adversely impact on either OS or PFS in patients undergoing allogeneic transplantation for haematological malignancies but it does have a significant impact on infection rates and hospitalisation of high BMI and obese patients. We recommend patients with high BMI should not be excluded from allogeneic transplantation however good supportive care should be undertaken and careful patient selection on the basis of comorbidity index in order to avoid the risks from the increased rates of infection.Response to Reviewers: I am really grateful for your comments The changes suggested by the reviewer has been incorporated in the materials and methods and also in the table with the patient characteristics(disease status at transplant, disease type, related unrelated donor equally distributed between the two groups) I have also added the D+100 mortality as well as the 1st year mortality for both groups Disease split (myeloid vs lymphoid showed similar results in both groups) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Abstract Bone marrow transplantation is frequently used as a consolidation therapy in patients with haematological malignancies to improve outcome of these patients.Obese individuals have larger absolute lean body and fat masses than non-obese individuals of the same age, gender and height, which might lead to altered This study shows that high BMI and obesity does not adversely impact on either OS or PFS in patients undergoing allogeneic transplantation for haematological malignancies but it does have a significant impact on infection rates and hospitalisation of high BMI and obese patients. We recommend patients with high BMI should not be excluded from allogeneic transplantation however good supportive 1