Search

Background\ud \ud The outcome of chemotherapy in patients older than 40 years with acute lymphoblastic leukaemia is poor and myeloablative allogeneic haematopoietic stem-cell transplantation (HSCT) has a high transplant-related mortality (TRM) in this age cohort. The aim of this study was to assess the activity and safety of reduced-intensity conditioned allogeneic HSCT in this patient population.\ud \ud \ud \ud Methods\ud \ud This was a single-arm, prospective study within the UKALL14 trial done in 46 centres in the UK, which recruited patients to the transplantation substudy. Participants in UKALL14 had B-cell or T-cell acute lymphoblastic leukaemia, were aged 25–65 years (BCR-ABL1-negative) or 18–65 years (BCR-ABL1-positive), and for this subcohort had a fit, matched sibling donor or an 8 out of 8 allelic matched unrelated donor (HLA-A, HLA-B, HLA-C, and HLA-DR). On June 20, 2014, the protocol was amended to allow 7 out of 8 matched unrelated donors if the patient had high risk cytogenetics or was minimal residual disease (MRD)-positive after the second induction course. Patients were given fludarabine, melphalan, and alemtuzumab (FMA; intravenous fludarabine 30 mg/m2 on days –6 to –2, melphalan 140 mg/m2 on day –2, and alemtuzumab 30 mg on day –1 [sibling donor] and days –2 and –1 [unrelated donor]) before allogeneic HSCT (aged ≥41 years patient pathway). Donor lymphocyte infusions were given from 6 months for mixed chimerism or MRD. The primary endpoint was event-free survival and secondary and transplantation-specific endpoints included overall survival, relapse incidence, TRM, and acute and chronic graft-versus-host disease (GVHD). This study is registered with ClinicalTrials.gov, NCT01085617.\ud \ud \ud \ud Findings\ud \ud From Feb 22, 2011, to July 26, 2018, 249 patients (236 aged ≥41 years and 13 younger than 41 years) considered unfit for a myeloablative allograft received an FMA reduced-intensity conditioned HSCT. 138 (55%) patients were male and 111 (45%) were female. 88 (35%) participants received transplantations from a sibling donor and 160 (64%) received transplantations from unrelated donors. 211 (85%) participants had B-precursor acute lymphoblastic leukaemia. High-risk cytogenetics were present in 43 (22%) and another 63 (25%) participants were BCR-ABL1-positive. At median follow-up of 49 months (IQR 36–70), 4-year event-free survival was 46·8% (95% CI 40·1–53·2) and 4-year overall survival was 54·8% (48·0–61·2). 4-year cumulative incidence of relapse was 33·6% (27·9–40·2) and 4-year TRM was 19·6% (15·1–25·3). 27 (56%) of 48 patients with TRM had infection as the named cause of death. Seven (15%) of 48 patients had fungal infections, 13 (27%) patients had bacterial infections (six gram-negative), and 11 (23%) had viral infections (three cytomegalovirus and two Epstein-Barr virus). Acute GVHD grade 2–4 occurred in 29 (12%) of 247 patients and grade 3–4 occurred in 12 (5%) patients. Chronic GVHD incidence was 84 (37%) of 228 patients (50 [22%] had extensive chronic GVHD). 49 (30%) of 162 patients had detectable end-of-induction MRD, which portended worse outcomes with event-free survival (HR 2·40 [95% CI 1·46–3·93]) and time-to-relapse (HR 2·41 [1·29–4·48]).\ud \ud \ud \ud Interpretation\ud \ud FMA reduced-intensity conditioned allogeneic HSCT in older patients with acute lymphoblastic leukaemia in first complete remission provided good disease control with moderate GVHD, resulting in better-than-expected event-free survival and overall survival in this high-risk population. Strategies to reduce infection-related TRM will further improve outcomes.\ud \ud \ud \ud Funding\ud \ud Cancer Research UK.

A new one-dimensional coordination polymer [(N2H5)2Co(HPO4)2] was synthesized by slow evaporation method and characterized by means of single-crystal X-ray diffraction, Fourier Transform Infrared Spectroscopy (FTIR) and Thermogravimetric Analysis (TGA). Its catalytic activity was tested using UV–visible absorption measurements. The compound crystallizes in the monoclinic system (S.G: P21/c) with the cell parameters (Å, °): a = 5.3665(3), b = 11.1271(6), c = 7.7017(4), β = 104.843(4), V = 444.55(4) Å3 and Z = 2. The crystal structure, consisting of a linear chain, is made of rings of [CoN2O4] octahedra and [PO3(OH)] tetrahedra sharing vertices via oxygen atoms coordinated to cobalt centers. The rings are linked to chains running along [100] and form thereby polymeric chains that are connected by hydrogen bonds in a three-dimensional arrangement. The FTIR spectroscopy shows the expected bands of hydrazine and phosphate groups. The thermal behavior consists mainly of the loss of hydrazine moieties leading thus to the formation of anhydrous cobalt phosphate. The phosphate complex exhibits efficiency in catalytic oxidation and degradation of methylene blue dye. The ac magnetic susceptibility shows a peak indicating antiferromagnetic order with a Néel temperature of 5.5 K. Fitting the Curie-Weiss equation to the ac magnetic susceptibility above 50 K gives the average Curie-Weiss Constant to be −11.8 K.