Mobilization and collection of peripheral blood stem cells in healthy donors: risks, adverse events and follow-up.

Allogeneic haematopoietic stem cell transplantation is the choice treatment for many haematological malignancies. Granulocyte-colony-stimulating factor (G-CSF) has been widely used to mobilize stem cells into the peripheral blood from healthy siblings or volunteer unrelated donors. To a large extent, the use of mobilized peripheral blood haematopoietic stem cells has replaced marrow-derived stem cells as the preferred source of donor haematopoietic stem cells. Clinicians have been aware since the first clinical use, that administration of G-CSF, even in a single short course, could possibly be a risk for healthy donors either in short-term or as a delayed effect. The immediate side effects of G-CSF have been established for a long time, most of them are frequent but transient, self-limited and without long-term consequences. Questions have been raised about potential long-term adverse effects such as an elevated risk of haematological malignancies after G-CSF administration. More long-term safety data from registries are needed to adequately evaluate such a relationship. Our objective in this article is to provide an in-depth review of reported adverse events associated with the use of G-CSF in healthy donors and to focus attention on unanswered questions related to their long-term follow-up.

[HLA typing, analysis methods, and clinical applications]. / Typage HLA, méthodes d'analyses et applications cliniques.

The polygenic HLA system is a well known region of the human genome. Its main function is to present antigenic peptides to the immune system and thereby regulate induction of immune responses. Extensive genetic polymorphisms characterize some HLA genes. Initially, genetic variations were analyzed by a serological typing technique (microlymphocytotoxicity). The introduction of polymerase chain reaction (PCR) in the mid-1980s led the development of a variety of methods that use molecular biology. An international nomenclature, regularly updated, governs the names of HLA antigens defined by serology as well as of HLA alleles. Knowledge of the specific polymorphisms of individuals is essential in organ and stem cell transplantation and highly useful in disease association studies.

Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study.

We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.

[Graft vs host disease]. / La réaction du greffon contre l'hôte.

Graft vs host disease is a serious immunological complication of allogeneic haematopoietic cell transplantation, leading to a significant morbidity and mortality. It occurs when donor T lymphocyte react to foreign host cells. The physiopathology is a more complex process implicating host tissues damage caused by the conditioning regimen, cytokines, cellular effectors implicated in the immune response such as donor lymphocytes T, antigen presenting cells and mechanisms of apoptosis. This review focuses on the physiopathological basis, risk factors, clinical aspects; prevention and current management strategies to treat graft vs host disease. Recent developments in our understanding of this bone marrow transplantation complication have profoundly influenced the practice of allogeneic haematopoietic cell transplantation. There is a growing realisation of the importance of a graft vs leukaemia effect, strategy, which has encouraged the development of less conditioning regimens. Segregation between graft vs host effect and graft vs leukaemia effect is a key challenge, and could lead to new efficient and specific immunotherapy.

[Transfusion related acute lung injury (TRALI): an unrecognised pathology]. / Syndrome de détresse respiratoire aiguë post-transfusionnel: un pathololgie méconnue.

Transfusion related acute lung injury (TRALI) is a rare but potentially severe complication of blood transfusion, manifested by pulmonary oedema, fever and hypotension. The signs and symptoms are often attributed to other clinical aspects of a patient's condition, and therefore, TRALI may go unrecognised. It has been estimated to be the third cause of transfusion related mortality, so it should be better diagnosed. Cases are related to multiple blood units, such as white blood cells, red blood cells, fresh frozen plasma, platelets or intravenous immunoglobulins. Physiopathology of TRALI is poorly understood, and still controversial. It is often due to an immunological conflict between transfused plasma antibodies and recipients' blood cells. These antibodies are either HLA (class I or II) or granulocyte-specific. They appear to act as mediators, which result in granulocytes aggregation, activation and micro vascular pulmonary injury. Lipids or cytokines in blood units are also involved as TRALI priming agents. Diagnosis is based on antibody screening in blood components and on specific-antigen detection in the recipient. The screening of anti-HLA or anti-granulocytes is recommended as part of prevention for female donors who had been pregnant. Preventative measures should also include leucoreduction and measures to decrease the amount of priming agents in blood components. In this article, we summarise what is known about TRALI, and we focus attention on unanswered questions and controversial issues related to TRALI.