Maria Grazia Orofino

Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000–2010

Allogeneic hemopoietic stem cell transplantation (HSCT) is the only method currently available to cure transfusion-dependent thalassemia major that has been widely used worldwide. To verify transplantation distribution, demography, activity, policies and outcomes inside the European Group for Blood and Marrow Transplantation (EBMT), we performed a retrospective non-interventional study, extracting data from the EBMT hemoglobinopathy prospective registry database. We included 1493 consecutive patients with thalassemia major transplanted between 1 January 2000 and 31 December 2010. In total, 1359 (91%) transplants were performed on patients <18 years old, 1061 were from a human leukocyte Ag-identical sibling donor. After a median observation time of 2 years, the 2-year overall survival (OS) and event-free survival (EFS; that is, thalassemia-free survival) were 88±1% and 81±1%, respectively. Transplantation from a human leukocyte Ag-identical sibling offered the best results, with OS and EFS of 91±1% and 83±1%, respectively. No significant differences in survival were reported between countries. The threshold age for optimal transplant outcomes was around 14 years, with an OS of 90–96% and an EFS of 83–93% when transplants were performed before this age. Allogeneic HSCT for thalassemia is a curative approach that is employed internationally and produces excellent results.

Fetal HLA typing in β thalassaemia: implications for haemopoietic stem-cell transplantation

Stem-cell transplantation can cure beta thalassaemia. We aimed to assess whether fetal HLA typing done early in the pregnancy of couples who were at risk of beta thalassaemia could provide an alternative to pregnancy termination if the prospect of a bone-marrow transplantation from a family member was available. In our clinic in Sardinia, we did fetal HLA typing for 49 couples at risk of having a baby with beta thalassaemia. Two affected children were born and successfully received a transplantation from a family donor. Five non-affected fetuses were HLA compatible with an affected sibling and their cord blood was harvested for a future transplantation.

Acute lymphoblastic leukemia in a child with constitutional ring chromosome 21

This report describes a case of acute lymphoblastic leukemia with non-B, non-T, common acute lymphocytic leukemia antigen-positive blasts in a 13-year-old child with constitutional ring chromosome #21. Because ring chromosome #21 is a rare chromosomal disorder, it is likely that the leukemia transformation is related to the chromosomal anomaly.

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.

Long‐term survival of beta thalassemia major patients treated with hematopoietic stem cell transplantation compared with survival with conventional treatment

Allogeneic hematopoietic stem cell transplantation (HSCT) in thalassemia remains a challenge. We reported a single‐centre case‐control study of a large cohort of 516 children and adult patients treated with HSCT or blood transfusion support and iron chelation therapy; 258 patients (median age 12, range 1‐45) underwent sibling (67%) or unrelated (33%) HSCT; 97 patients were adults (age ≥ 16 years). The median follow‐up after HSCT was 11 years (range 1‐30). The conditioning regimen was busulfan (80.6%) or treosulfan‐based (19.4%). A cohort of 258 age‐sex matched conventionally treated (CT) patients was randomly selected. In transplanted patients the 30‐year overall survival (OS) and thalassemia‐free survival (TFS) were 82.6 ± 2.7% and 77.8 ± 2.9%, compared to the OS of 85.3 ± 2.7% in CT patients (P = NS); The incidence of grade II‐IV acute and chronic graft versus host disease (GvHD) was 23.6% and 12.9% respectively. The probability of rejection was 6.9%. Transplant‐related mortality (TRM) (13.8%) was similar to the probability of dying of cardiovascular events in CT patients (12.2%). High‐risk Pesaro score (class 3) was associated with lower OS (OR = 1.99, 95% C.I.=1.31‐3.03) and TFS (OR = 1.54, 95% C.I.=1.12‐2.12). In adult patients, the 23‐years OS and TFS after HSCT were 70 ± 5% and 67.3 ± 5%, compared to 71.2 ± 5% of OS in CT (P = NS). Finally, treosulfan was associated with lower risk of acute GvHD (P = .004; OR = 0.28, 95% C.I.=0.12‐0.67). In conclusion, the 30‐year survival rate of ex‐thalassemia patients after HSCT was similar to that expected in CT thalassemia patients, with the vast majority of HSCT survivors cured from thalassemia.

Reassessing the approach to informed consent: the case of unrelated hematopoietic stem cell transplantation in adult thalassemia patients

IntroductionThe informed consent process is the legal embodiment of the fundamental right of the individual to make decisions affecting his or her health., and the patient’s permission is a crucial form of respect of freedom and dignity, it becomes extremely important to enhance the patient’s understanding and recall of the information given by the physician. This statement acquires additional weight when the medical treatment proposed can potentially be detrimental or even fatal. This is the case of thalassemia patients pertaining to class 3 of the Pesaro classification where Allogenic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment. Unfortunately, this kind of intervention is burdened by an elevated transplantation-related mortality risk (TRM: all deaths considered related to transplantation), equal to 30% according to published reports. In thalassemia, the role of the patient in the informed consent process leading up to HSCT has not been fully investigated. This study investigated the hypothesis that information provided by physicians in the medical scenario of HSCT is not fully understood by patients and that misunderstanding and communication biases may affect the clinical decision-making process.MethodsA questionnaire was either mailed or given personally to 25 patients. A second questionnaire was administered to the 12 physicians attending the patients enrolled in this study. Descriptive statistics were used to evaluate the communication factors.ResultsThe results pointed out the difference between the risks communicated by physicians and the risks perceived by patients. Besides the study highlighted the mortality risk considered to be acceptable by patients and that considered to be acceptable by physicians.ConclusionsSeveral solutions have been suggested to reduce the gap between communicated and perceived data. A multi-disciplinary approach may possibly help to attenuate some aspects of communication bias. Several tools have also been proposed to fill or to attenuate the gap between communicated and perceived data. But the most important tool is the ability of the physician to comprehend the right place of conscious consent in the relationship with the patient.