Marco Sanna

Long-term health-related quality of life evaluated more than 20 years after hematopoietic stem cell transplantation for thalassemia

The principal aim of our study was to investigate whether patients transplanted more than 20 years ago for β-thalassemia major had a different health-related quality of life (HRQoL) compared with the general population. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) were received from 109 ex-thalassemia patients who underwent hematopoietic stem cell transplantation (HSCT) during the 1980s and 1990s. Adjusted comparisons were performed separately for patient age at HSCT and the presence or absence of graft-versus-host disease (GVHD). Sociodemographic and clinical variables were also analyzed. The median age of our cohort at HSCT and the time of the survey was 12 years (range, 1-36) and 34 years (range, 21-48), respectively, with a median follow-up age of 22.8 years (range, 11.7-30.3). Statistical analysis of data collected more than 20 years after HSCT showed that the long-term HRQoL of ex-thalassemia patients was very similar to that of the general population. Clinical meaningful differences were only found for the general health (GH) scale (-8.9; 95% CI, -15.0 to 2.7, P = .005). Mental health, education level, employment status, marital status, living arrangements, and birth rate were compatible with normal living patterns. The development of GVHD and older age at transplantation were important impairing factors. Additional analyses performed to evaluate HRQoL in an age-sex-matched cohort of 124 patients receiving conventional treatment of β-thalassemia revealed poorer outcomes compared with the cohort of transplanted patients.

Interactions between killer immunoglobulin-like receptors and their human leucocyte antigen Class I ligands influence the outcome of unrelated haematopoietic stem cell transplantation for thalassaemia: a novel predictive algorithm.

In a study conducted on 114 patients undergoing unrelated donor haematopoietic stem cell transplantation (HSCT) for thalassaemia, we observed that the lack of activating killer immunoglobulin‐like receptors (KIRs) on donor natural killer (NK) cells significantly increased the risk of graft‐versus‐host disease (GvHD) [hazard risk (HR) 4·2, 95% confidence interval (CI) 1·7–10·1, P = 0·002] and transplantation‐related mortality (HR 4·7, 95% CI 1·6–14·2, P = 0·01). The risk of GvHD furthermore increased when recipients heterozygous for HLA‐C KIR ligand groups (C1/C2) were transplanted from donors completely lacking activating KIRs (HR 6·1, 95% CI 1·9–19·2, P = 0·002). We also found that the risk of rejection was highest when the recipient was homozygous for the C2 HLA‐KIR ligand group and the donor carried two or more activating KIRs (HR 6·8, 95% CI 1·9–24·4, P = 0·005). By interpolating the number of donor activating KIRs with recipient HLA‐C KIR ligands, we created an algorithm capable of stratifying patients according to the immunogenetic risk of complications following unrelated HSCT. In clinical practice, this predictive tool could serve as an important supplement to clinical judgement and decision‐making.

Risk of invasive fungal infection in patients affected by acute promyelocytic leukaemia. A report by the SEIFEM-D registry

Dr Mohanarasan Ratanam: wrote the paper. Professor Dr Visvaraja Subrayan: wrote up the case and proof read the manuscript. You Siang Ngim: contributed information from literature search. Assc. Prof. Nurliza Khalidin: performed literature research and proof read the manuscript. Mohanarasan Ratanam You Siang Ngim Nurliza Khalidin Visvaraja Subrayan Department of Ophthalmology, University of Malaya Medical Centre, Jalan University, Kuala Lumpur, and Department of Ophthalmology, Sultanah Fatimah Hospital, Muar, Johor, Malaysia. E-mail: mohanslayer@gmail.com

Absence of activating killer immunoglobulin-like receptor genes combined with hepatitis C viral genotype is predictive of hepatocellular carcinoma

Killer immunoglobulin-like receptors and their human leukocyte antigen class I ligands have a critical role in natural killer cell response to viral pathogens and tumors. To investigate whether killer immunoglobulin-like receptor genes could influence the chronic course of hepatitis C virus infection and/or progression to hepatocellular carcinoma we retrospectively analyzed a cohort of 228 patients transplanted for hepatitis C virus-induced cirrhotic end stage liver disease, combined or not with hepatocellular carcinoma. We found that patients completely lacking activating killer immunoglobulin-like receptor genes had a high risk of developing hepatocellular carcinoma. Hepatitis C viral genotype and viral load are other risk factors that can influence the course of chronic hepatitis C virus infection. In our study, the risk conferred by hepatitis C viral genotypes was enhanced in patients lacking activating killer immunoglobulin-like receptors. These results point to an important role for activating killer immunoglobulin-like receptors in the control of hepatitis C virus infection and progression to hepatocellular carcinoma. In clinical practice, assessment of killer immunoglobulin-like receptor and hepatitis C viral genotype combinations should allow for more accurate monitoring of patients with chronic hepatitis C virus infection.

Daunorubicin, Cytarabine, and Cladribine Regimen Plus Radiotherapy and Donor Lymphocyte Infusion for Extramedullary Relapse of Acute Myeloid Leukemia after Hematopoietic Stem Cell Transplantation

Myeloid sarcoma is a rare tumor consisting of myeloid blasts that involve anatomic sites outside the bone marrow. Fatal prognosis is inevitable in patients with extramedullary relapse after hematopoietic stem cell transplantation (HSCT), and no standard treatments are available yet. We report the first case of extramedullary relapse after HSCT treated with a combination of daunorubicin, cytarabine, and cladribine (DAC) regimen plus radiotherapy and donor lymphocyte infusion (DLI). This treatment induced a new and durable remission in our patient. The favorable toxicity profile and the reduced cost make this combination worthy of further investigations.

Glucose-6-phosphate dehydrogenase deficiency and risk of invasive fungal disease in patients with acute myeloid leukemia

Abstract Invasive fungal diseases (IFD) are still a leading cause of morbidity and mortality in patients with acute myeloid leukemia (AML). Glucose-6-phosphate dehydrogenase is an enzyme that leads to the production of NADPH, required to destroy microorganisms in the respiratory burst reaction of white blood cells. We evaluated the role of G6PD deficiency in susceptibility of IFD in 108 AML patients undergoing intensive chemotherapy. In all, 28 patients harbored G6PD deficiency (G6PD−), whereas 80 were normal (G6PD +). Incidence of IFD was significantly higher in G6PD− patients compared to G6PD + patients (35.7% vs. 5%, p = .0002, OR = 10, 95% CI = 2.96–37.5). Higher risk of mold infections (17.9% vs. 5%, p = .048, OR = 4.1, 95% CI = 1.0–16.6) and Candida sepsis (17.9% vs. 0%, p = .0009, OR = 37.68, 95% CI =2.0–707.1) was observed in G6PD − patients. The evaluation of G6PD activity may help to identify AML patients at higher risk of IFD, allowing to design more intensive surveillance and therapeutic strategies.

Successful and safe stem cell mobilization using plerixafor in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Treatment of patients aff ected by Philadelphia chromosome- positive acute lymphoblastic leukemia (PhALL) continues to be problematic in spite of the better complete response rates (75 - 95%) achieved with induction regimens based on tyrosine kinase inhibitors (TKIs), used either alone or in combination with conventional cytotoxic chemotherapy agents (1). Th e presence of the Philadelphia chromosome (Ph) remains a primary indication for hematopoietic stem cell transplant (HSCT), but for patients lacking a suitable donor other post-induction strategies need to be investigated. Reports published during the imatinib era, albeit limited in size and number, suggest that autologous HSCT needs to be reconsidered for patients with Phacute lymphoblas- tic leukemia (ALL) with low or negative molecular residual disease (MRD) at the end of remission-induction therapy (2,3). Unfortunately, patients older than 60 years and

Safe fluoroquinolones prophylaxis in blood cancer patients with chemotherapy-induced neutropenia and Glucose-6-Phosphate-Dehydrogenase deficiency

Bacterial infections are the leading causes of morbidity and mortality in haematologic patients with chemotherapy‐induced neutropenia. The only strategy shown to be effective in reducing febrile neutropenia incidence is fluoroquinolone prophylaxis, but the safety of this class of drugs in patients with glucose‐6‐phosphate dehydrogenase deficiency (G6PD−), the most common human enzyme defect, is still controversial because of the claimed association with acute haemolytic anaemia.