clinicaltrials.gov Identifier: NCT01789762.

Summary:New approaches using nonmyeloablative-conditioning regimens have been developed to cause minimal procedure-related toxicity. Such novel therapeutic options are being explored with good preliminary results concerning feasibility and engraftment. However many aspects remain under-evaluated, and few data are available about viral and nonviral infections after these highly immunosuppressive regimens. We present our preliminary data on 21 patients receiving a highly immunosuppressive conditioning strategy, focusing on early infectious complications. Early viral infections before day 45, especially CMV, occurred at a high rate (65%). Furthermore, 33% of patients presented with late bacterial infections (predominately gram negative) although they were not neutropenic compared to conventional conditioning regimens. Although there is presently real interest in these new conditioning regimens which result in reduced immediate transplantrelated mortality, it is important that investigators be aware of these pitfalls which may secondarily increase transplant toxicity. Further studies are needed to confirm these findings. Bone Marrow Transplantation (2000) 26, 251-255. Keywords: allogeneic bone marrow transplantation; nonmyeloablative conditioning; cytomegalovirus; septicemia Allogeneic bone marrow transplantation (allo-BMT) has been successfully used to treat patients with hematological malignancies.1 Due to the increased risk of conditioning regimen-related toxicities and graft-versus-host disease (GVHD), this procedure is generally limited to young patients with good performance status.2,3 Despite its hazardous immediate and late complications, allo-BMT offers an important antileukemic and antitumoral advantage due to alloreactivity against host tumor cells. 4,5 The immune reactions between donor-derived immunocompetent T lymphocytes and host-type tumor cells have been well established to be the major antitumor agent in allo-BMT. supporting the so-called graft-versus-leukemia (GVL) effect includes the higher risk of relapse following T celldepleted or syngeneic transplants. 6,7 Furthermore, donor lymphocyte infusions (DLI) may re-induce remissions in many patients relapsing after allo-BMT. 8 Recently, new approaches using nonmyeloablative-conditioning regimens have been developed to obtain minimal procedure-related toxicity.9,10 These approaches aim at extending the use of allo-BMT to patients who are not eligible for high-dose chemotherapy or total body irradiation by increasing the immunosuppressive aspect of the preparation. Such novel therapeutic options are being explored at the moment with good preliminary results concerning feasibility and engraftment. 9,10

This survey demonstrates that AEs occurring in the setting of DMSO-reduced HPC grafts are directly related to the amount of granulocytes and thus emphasizes the need for high-quality apheresis products so as to improve the safety of HPC infusion.

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Summary:Case reportA 38-year-old man (blood group A+; phenotype A 38-year-old man, blood group A+, was allotransplanted for multiple myeloma from his fully matched D+C+E−c+e+K−) was allotransplanted for multiple myeloma from his fully HLA-matched sister (blood group O+, sister, blood group O+. Anti-A antibodies IgG and IgM titres of the donor were low. Allogeneic peripheral blood phenotype D+C−E−c+e+K−). Recipient and donor ABO groups were determined twice using RBC grouping test and stem cells were harvested by leukapheresis after subcutaneous administration of G-CSF. Rapid serum grouping test. No unexpected alloantibody was identified. Anti-A antibodies IgG and IgM titres of the engraftment occurred since 5.6 × 10 9 /l leukocytes were achieved on day +9 post-transplant. At this time a sevdonor were low (both 1/8). Allogeneic peripheral blood stem cells were harvested by leukapheresis after subcutaneere immune haemolytic syndrome occurred and direct antiglobulin test was positive (IgG and C3d). Elution ous administration of G-CSF (granocyte, kindly provided by Bellon, Neuilly, France) (CD34 + 3.5 × 10 6 /kg; CD3 + showed an anti-A specificity. Evolution was rapidly unfavourable related to multiorgan failure. The patient 410 × 10 6 /kg; CD19 + 79 × 10 6 /kg). The conditioning regimen consisted of cyclophosphamide (60 mg/kg) and TBI; died on day +20 post-transplant. Keywords: ABO incompatibility; allogeneic peripheral prevention of GVHD was provided by cyclosporin A (CsA) and methylprednisolone. No deplasmatisation of the blood stem cell transplantation APBSC was performed since anti-A antibody titre of the donor was low. Rapid engraftment occurred since 500/mm 3 and 5600/mm 3 leukocytes were achieved on day +8 and +9, Allogeneic bone marrow transplantation can be successrespectively. Two transfusions of phenotyped and irradiated fully performed despite ABO incompatibility between the A+ RBC and one irradiated platelet transfusion of group donor and recipient. Major incompatibility may cause a A+ were given to the patient on day +7 when Hb was severe haemolytic transfusion reaction at the time of BMT 7.1 g/dl and platelet counts were 6000/mm 3 . On day +9, a due to interaction of donor type RBC with pre-existing severe immune haemolytic syndrome occurred: acute anehost-derived isohaemagglutins. This complication can be mia, backpain, elevation of bilirubin, LDH and serum prevented easily by removing RBC from the marrow graft.creatinin. Direct antiglobulin test was positive (IgG and On the other hand minor incompatibility, where donorC3d) (Figure 1). Serum testing showed the presence of antiderived antibodies are directed against ABO antigens of the A alloantibodies. The saline indirect antiglobulin test recipient erythrocytes, may lead to delayed immune haeshowed an anti-A specificity and elution in LISS (low ionic molysis caused by transient antibody production from strength saline) solution revealed strong reactivity anti-A donor immunocompetent lymphocytes. This complication (++++). Group O RBC with original r...

The CytoMate device allows for a significant reduction in DMSO infusion, with a diminished frequency and severity of immediate side effects and does not compromise neutrophil or PLT engraftment.

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Cytomegalovirus (CMV) infection is a serious complication that may occur in the weeks or months following bone marrow transplantation. However, both Ganciclovir and the CMV infection itself can cause marrow toxicity, notably neutropenia, that may consequently expose these immunosuppressed patients to life-threatening bacterial and/or fungal infections. The aim of this retrospective study was to identify factors associated with the occurrence of grade III-IV neutropenia among patients receiving pre-emptive Ganciclovir therapy after allogeneic stem cell transplantation at our Institution. We identified 547 consecutive patients transplanted from January 2005 to June 2011 at our Institution. In all, 190 patients (35%) presented with CMV reactivation of whom 30 patients (5%) were excluded from the analysis because they already had neutropenia at the time of reactivation. Finally, 160 (29%) patients were analysed. According to multivariate analysis, at the time of treatment initiation, the risk factors significantly associated with a grade III-IV Ganciclovir-related neutropenia included a high viral load (hazard ratio (HR) = 2.68, 95% CI 1.25-5.737, p 0.01); an absolute neutrophil count >3000 was a protective factor (HR = 0.26, 95% CI 0.125-0.545, p <0001) whereas serum creatinine >2 mg/dL was associated with higher Ganciclovir-related neutropenia (HR = 2.4, 95% CI 1.11-5.17, p 0.002). This large analysis revealed three risk factors for Ganciclovir-related neutropenia among patients with CMV reactivation after allogeneic stem cell transplantation; prompt identification of patients at risk when antiviral therapy is started may allow clinicians to adopt adequate preventive measures, so reducing the morbidity and mortality associated with CMV reactivation.