[Transfusion in autologous and allogenic hematopoietic stem cell transplant: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Transfusion dans l'autogreffe et l'allogreffe de cellules souches hématopoïétiques chez l'adulte et l'enfant : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

The recommendations of the French Health and Drug Safety Authorities (HAS/ANSM-Haute Autorité de santé/Agence nationale de sécurité du médicament) are known, but there are always new developments underway. With regards to CMV suppression, there is the introduction of platelet glycoprotein Ia and the Intercept (Amotosalem+UVA) inactivation method which addresses bacterial risk. The irradiation of platelets is included in the recommendations to ensure HEV-negative plasma post allograft. In terms of blood transfusion safety, these measures as well as the broader spectrum of Ia, particularly for arboviruses, are a real breakthrough. The survey conducted in clinical services and the services providing blood products for transfusion along with a literature review have shown that several improvements need to be made. The first is a reduction of transfusions of concentrated red blood cells with introduction at a threshold of 7g/dL during hospitalization of patients without a fragile clinical status. The second improvement would address transfusion of refractory thrombocytopenia, encouraging an increase in discussion between clinicians and those conducting the transfusion in order to consider different etiologies and to identify appropriate care protocols. Third would be the need for the transmission of information between the transplantation doctors and blood transfusion specialists in order to define an approach to transfusion care adapted to the patient's situation. It is important to inform and educate patients about transfusion protocols post allotransplant or autotransplant. It must be clearly communicated to patients that they should always have on their person their blood group documentation. This is especially true when receiving care for a hemopathy or an autologous transplant. If undergoing an allogeneic transplant, patients should also carry transfusion guidelines post autotransplant or post allotransplant along with the phone numbers for the stem cell transplantation department and the blood transfusion center responsible for their care.

Platelet transfusion refractoriness in patients with acute myeloid leukemia treated by intensive chemotherapy.

Platelet transfusion refractoriness (PTR) is a major adverse event in the management of acute myeloid leukemia (AML). In a series of 897 adult patients with AML receiving intensive chemotherapy, we identified 41 patients (4.8%) with PTR. PTR was more frequently observed in parous women, patients with extra-medullary disease, a low white blood cell count, an infection, or hemophagocytic syndrome. Among the 31 patients with anti-human leucocyte antigen (HLA) antibodies, an HLA-matched donor was identified for 18 patients (58.1%). Median time between diagnosis of PTR and the first HLA-matched transfusion was 12.5days. HLA-matched transfusions induced a significant increment in platelet counts in 37% of cases. Thrombopoietin receptor agonists were given to 10 patients but did not shorten the duration of thrombocytopenia, reduce severe bleeding, or early death. Grade 3-4 bleeding events during induction, early death caused by bleeding, and death caused by bleeding at any time were significantly greater in patients that had platelet transfusion refractoriness (22% vs. 4.1%, P<0.0001; 12.2% vs. 1.4%, P=0.0006; and 24.4% vs. 5.3%, P<0.0001; respectively). PTR during chemotherapy for AML significantly increased the risk of early and late deaths caused by a severe bleeding event. Improved understanding of platelet destruction is needed to design mechanism-based therapeutic strategies.

Treatment of large plasma volumes using specific immunoadsorption to desensitize ABO-incompatible kidney-transplant candidates.

BACKGROUND: ABO-incompatible (ABOi) kidney-transplantation has very good long-term results, i.e. similar to those observed for living-kidney ABO-compatible transplantation. This is because patients are desensitized at pretransplant using apheresis and rituximab therapy, with tacrolimus-based immunosuppression. OBJECTIVES: To assess the efficacy of a single, pretransplant (Day -1), specific immunoadsorption session using Glycosorb® columns (anti-A or anti-B; Glycorex Sweden) to treat large volumes of plasma (up to 18 L). PATIENTS AND METHODS: Prospective single-center study evaluating 12 consecutive patients (6 males), aged 40 (23-59) years. Incompatibilities were A into 0 (8), B into 0 (3), and AB into 0 (1). Pretransplant desensitization relied on rituximab (D-30), tacrolimus, mycophenolic acid, and steroids (all started on D-13), and a single session of specific immunoadsorption on D-1. Immunoadsorption was coupled in tandem with a hemodialysis session. RESULTS: Overall, 15 L (11-18) of plasma were treated per patient, i.e., 0.2 (0.11-0.36 L/kg). Isoagglutinin titers were 1/16 (1/5-1/64) before the procedure, decreasing after 6 hours to 1/5 (1/1-1/16 P = 0.008), and to 1/2 (1/1-1/8; P = 0.05) at completion of the session. The next day, i.e., the day of transplantation, there was no rebound of isoagglutinins [1/4 (1/1-1/5); P = ns]. The procedure was well tolerated with no side-effects and no significant changes in hemoglobin level, platelet counts, fibrinogen, or albumin levels. CONCLUSIONS: For ABOi kidney-transplantation, a single, longer, specific immunoadsorption session was very efficient at 1-day pre-transplantation with no rebound. These results should be confirmed when isoagglutinin titers are higher (≥120).

Early post-transplant complications following ABO-incompatible kidney transplantation.

BACKGROUND: Living-kidney transplantation is increasing because of the scarcity of kidneys from deceased donors and the increasing numbers of patients on waiting lists for a kidney transplant. Living-kidney transplantation is now associated with increased long-term patient- and allograft-survival rates. OBJECTIVES: The purpose of this retrospective study was to identify, in a cohort of 44 ABO-incompatible (ABOi) live-kidney transplant patients, the main complications that occurred within 6 months post-transplantation, and to compare these findings with those from 44 matched ABO-compatible (ABOc) live-kidney transplant patients who were also from our center. PATIENTS AND METHODS: This single-center retrospective study assessed post-transplantation complications in 44 ABO-i versus 44 matched ABO-c patients. All patients were comparable at baseline except that ABO-i patients had greater immunological risks. RESULTS: During the 6-month post-transplant period, more ABO-i patients presented with postoperative bleeds, thus requiring significantly more blood transfusions. Bleeds were associated with significantly lower values of fibrinogen, platelets, prothrombin time, and hemoglobin levels. Surgical complications, patient- and graft-survival rates, and kidney-function statuses were similar between both groups at 6 months post-transplantation. CONCLUSIONS: We conclude that impairment of hemostatic factors at pre-transplant explained the increased risk of a post-transplant bleed in ABO-i patients.

Successful Transplantation in ABO- and HLA-Incompatible Living Kidney Transplant Patients: A Report on 12 Cases.

Few studies have assessed the outcomes of ABOi/HLAi living-kidney transplantation. We report a single-center experience of 12 ABOi/HLAi living-kidney recipients. Twenty-seven donor-specific alloantibodies (DSAs) (1-6 per patient) were found with fluorescence intensities of 1500-15 000. Desensitization was based on IVIg, two doses of rituximab (375 mg/m2 ), tacrolimus-based (0.2 mg/kg) immunosuppression (started on day-10 pretransplant), and 11 (6-27) pretransplant apheresis sessions (plasmapheresis, specific or semi-specific immunoadsorption). By day 0, 17 of the 27 DSAs had become undetectable. After 19 (3-51) months, patient- and graft-survival rates were 100% and 91.6%, respectively. One patient had an acute humoral rejection whereas three had a chronic antibody-mediated rejection (CAMR). At the last follow-up, kidney biopsies were nearly normal in seven cases (58.3%) and renal function was excellent except for the three cases of CAMR. Four patients had a BK virus infection. We conclude that ABOi/HLAi living-kidney transplantation is a reasonable option for highly sensitized patients.

Pilot conversion trial from mycophenolic acid to everolimus in ABO-incompatible kidney-transplant recipients with BK viruria and/or viremia.

Immunosuppression using everolimus (EVR) plus low-dose tacrolimus (Tac) is commonly used in organ transplantation. EVR has potential antiviral effects. Herein, the long-term outcomes and impacts of Tac-EVR on the BK virus are reported in ABO-incompatible kidney-transplant recipients. The initial immunosuppressive regimen combined steroids, Tac, and mycophenolic acid (MPA). At a median of 141 (34-529) days post-transplantation, seven stable ABO-incompatible kidney-transplant recipients were converted from MPA to EVR because of active BK replication, and compared with a reference group of fourteen ABO-incompatible patients receiving classical Tac plus MPA. At 1 month before conversion, at 1, 3 months after, and at last follow-up, clinical and biological parameters were monitored. The median time from conversion to the last follow-up was 784 (398-866) days. Conversion to EVR caused no change to rejection episodes or immunological status (isoagglutinin titers, anti-HLA antibodies). At last follow-up, median eGFR was similar in the Tac-MPA versus Tac-EVR group (40 [range: 14-56] vs. 54.5 ml/min/1.73 m(2) [range: 0-128], P = 0.07). The major adverse event was dyslipidemia. Interestingly, conversion from MPA to EVR decreased BK viral load in five patients. ABO-incompatible kidney-transplant recipients with an active BK virus infection may benefit from conversion to EVR.