Treatment-free remission in CML patients with additional chromosome abnormalities in the Philadelphia-positive clone or variant Philadelphia translocations.

Probability of treatment-free remission (TFR) in CML patients with additional chromosomal abnormalities (ACA) in the Philadelphia-positive clone or variant Philadelphia translocations (ACA/Var-Ph group, blue panel), in those with no cytogenetic abnormality other than the classical Philadelphia translocation (c-Ph group, green panel) and in the subgroups of CML patients with high-risk ACA (HR-ACA, yellow panel) and Var-Ph (red panel).

Haploidentical Transplant with Post-Transplant Cyclophosphamide for Acute Myeloid Leukaemia and Myelodysplastic Syndromes Patients: The Role of Previous Lines of Therapy.

Background: Allogeneic haematopoietic stem-cell transplant is an option, potentially curative, for high-risk acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients. Post-transplant cyclophosphamide administration allows for the selection of haploidentical donors in patients who are eligible for the procedure but do not have a fully matched donor since it can overcome the HLA barrier. There is still an active debate on whether intensifying the conditioning regimen is necessary with haploidentical donors when peripheral blood stem cells are used as the graft source. Herein, we report our decennial experience of haploidentical stem-cell transplant using peripheral blood stem cells (haplo-PBSC) at King's College Hospital. Objectives: The primary objective was to evaluate overall survival (OS) following haplo-PBSC. Secondary objectives were total OS for patients with less than two previous lines of therapy, OS according to cytomegalovirus (CMV) reactivation, incidence of transplant-related mortality (TRM), graft-versus-host disease (GVHD) and GVHD-relapse-free survival (GRFS). Results: One-year and three-year total OS were 62% and 43%, respectively, with a median OS of 22 months. One-year and three-year OS for patients with ≤2 and those with >2 previous lines of therapy were 72% and 55%, and 60% and 22%, respectively (p-value=0.04). The median OS in patients with >2 previous and ≤2 lines of therapy was 16 and 49 months, respectively. Cumulative incidence (CI) of relapse was 25% with a median time to relapse of 5 months (range 1 - 38 months). Conclusions: Haploidentical haematopoietic stem-cell transplant is potentially curative in chemosensitive AML and MDS and offers a high rate of prolonged remission. Our cohort further confirms the role of consolidative haploidentical transplant in patients in complete remission and highlights that patients with heavily pre-treated disease may not benefit from this strategy.

Myeloablative Dose of Busulfan and Fludarabine Combined with In Vivo T Cell Depletion Is Safe and Effective Conditioning for Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative strategy for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The prediction of transplantation-related mortality (TRM) using the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score and an arbitrary upper age limit of 55 years for administering myeloablative conditioning (MAC) are common strategies to ensure a safe procedure. The use of reduced-toxicity conditioning regimens is an additional approach to providing safe and effective myeloablation. Herein we report the outcome of AML and MDS patients conditioned with fludarabine and a myeloablative dose of busulfan (FB4) stratified by age and HCT-CI score. The primary objective was overall survival (OS) for patients age ≥55 years. Secondary objectives were total OS, TRM, graft-versus-host disease (GVHD), and GVHD, relapse-free survival (GRFS). The 2 year OS was 72% in patients age <55 and 51% in patients age ≥55. In patients age ≥55 with an HCT-CI <2, the estimated 2 year OS was 64%, with median OS not reached. In those with HCT-CI ≥2, the 2-year OS was 43%, with a median OS of 14 months. The total cumulative incidence of relapse was 30% regardless of age or HCT-CI score. FB4 conditioning regimen offers a high rate of prolonged remission with a relapse rate similar to that reported in previous studies. These positive outcomes suggest that this conditioning platform can be offered to patients age ≥55 years in the absence of comorbidities, and that age should not be the sole determinant of conditioning intensity.

Lymphoid blast crisis after prolonged treatment-free remission in chronic myeloid leukaemia after tyrosine kinase inhibitor de-escalation during the COVID-19 pandemic.

During the COVID-19 pandemic, access to health services has been considerably restricted and furthermore, patients have been reluctant to attend for routine monitoring, and this may have had a negative impact in the management of patients affected with haematological disorders. Sudden blast crisis in chronic myeloid leukaemia is categorized as a rapid onset of blastic phase, after a documented 'optimal' response to tyrosine kinase inhibitor (TKI) therapy and within 3 months of a normal complete blood count. Herein, we describe a case of patient who developed sudden blast crisis after TKI while in treatment-free remission.

Prevention of hemolytic transfusion reactions with intravenous immunoglobulin prophylaxis in U- patients with anti-U.

BACKGROUND: The U- phenotype is extremely rare and is found predominantly in black African populations at a frequency of between 0.2 and 1.7%. In European populations, U- units are therefore rare, with limited availability in the United Kingdom. Anti-U is clinically significant and is known to cause hemolytic transfusion reactions (HTRs) and hemolytic disease of the fetus and newborn. It has been suggested that intravenous immunoglobulin (IVIG) may be considered as an option among supportive therapy for urgent transfusion when clinically significant antigen-matched units are not available. We report three cases with anti-U transfused with least-incompatible RBC units, their outcomes, and their clinical management. STUDY DESIGN AND METHODS: Intravenous immunoglobulin was prescribed when least-incompatible units must be issued in patients with anti-U to ameliorate acute HTR and prevent the development of delayed HTR. We report the outcome of these cases. RESULTS: Of the case reports described, one patient with weak anti-U developed a delayed HTR after transfusion with incompatible units due to an anamnestic response. Two additional patients are described, with the use of IVIG as a precautionary measure to prevent the development of HTRs when transfused with antigen-positive incompatible units. No acute HTRs or delayed HTRs were noted upon follow-up. CONCLUSION: U- units are not always readily available and transfusion support requires close collaborative working among a multidisciplinary team. Transfusion with antigen-positive incompatible units with IVIG cover both ameliorates acute HTRs and prevents the development of delayed HTRs.