Pegfilgrastim compared with Filgrastim after autologous hematopoietic peripheral blood stem cell transplantation.

peer reviewedIn order to assess the effect of Pegfilgrastim on the duration of neutropenia and clinical outcome of patients after autologous peripheral blood stem cell (PBSC) transplantation, we compared 20 consecutive patients with lymphoma or multiple myeloma receiving a single 6-mg dose of Pegfilgrastim on day 1 posttransplant to an historical control group of 60 patients receiving daily Filgrastim 5 microg/kg starting on day 1 posttransplant. The duration of neutropenia was similar in the Pegfilgrastim group compared with the control group. There were no differences in time to neutrophil, erythroid, or platelet engraftment nor in the incidence of fever and infections. The duration of antibiotic therapy, transfusion support, and time to hospital discharge were similar in the two groups. However, after initial hematopoietic reconstitution, we observed significantly higher values of lymphocytes (e.g., 1,660+/-1,000 versus 970+/-460 on day 80, p=0.0002), neutrophils (e.g., 3,880+/-2,030 versus 2,420+/-1,500 on day 25, p=0.0004), reticulocytes (e.g., 148,160+/-90,590 versus 87,140+/-65,920 on day 25, p<0.0001), and platelets (e.g., 210,700+/-116,090 versus 150,240+/-58,230 on day 55, p=0.0052) up to day 100 in the Pegfilgrastim group compared with the Filgrastim group. These observations had no impact on clinical outcome of the patients after day 30 due to the low incidence of infectious events after engraftment in autologous PBSC transplantation. We conclude that the effect of Pegfilgrastim administrated on day 1 posttransplant is comparable to that of daily Filgrastim on initial hematopoietic reconstitution. The possibly superior effect of Pegfilgrastim on cell counts we observed after initial engraftment should be further tested in a prospective randomized trial

Recombinant human erythropoietin therapy after allogeneic hematopoietic cell transplantation with a nonmyeloablative conditioning regimen: low donor chimerism predicts for poor response.

peer reviewedPURPOSE: After allogeneic hematopoietic stem cell transplantation with nonmyeloablative conditioning (NMHCT), many patients experience prolonged anemia and require red blood cell (RBC) transfusions. We enrolled 60 consecutive patients undergoing NMHCT in a phase II trial to determine the optimal utilization of recombinant human erythropoietin (rHuEPO) therapy in this setting. PATIENTS AND METHODS: The first 14 NMHCT recipients did not receive rHuEPO (control group). Nineteen patients were scheduled to start rHuEPO on day 0 (EPO group 2) and 27 patients on day 28 after the transplant (EPO group 1). RHuEPO was administered subcutaneously once weekly at a dose of 500 U/kg/wk with the aim of achieving hemoglobin (Hb) levels of 13 g/dL. The 3 groups were well balanced for major characteristics. RESULTS: During the first month (p < 0.0001) as well as days 30 to 100 (p < 0.0001) and days 100 to 180 (p < 0.0001), Hb values were higher in patients receiving rHuEPO compared to those not receiving it. However, transfusion requirements were significantly decreased only in the first month in EPO group 2 (p = 0.0169). T-cell chimerism above 60% on day 42 was the best predictor of Hb response (p < 0.0001) or Hb correction (p = 0.0217), but myeloid chimerism above 90% also predicted for Hb response (p = 0.0069). Hb response was also decreased in patients receiving CD8-depleted grafts and increased in the few patients not receiving TBI, but only in univariate analysis. CONCLUSIONS: Anemia after NMHCT is sensitive to rHuEPO therapy, but less so than after conventional allogeneic HCT. RHuEPO decreases transfusion requirements only in the first 30 days posttransplant. T-cell chimerism below 60% on day 42 impaired Hb response, suggesting possible inhibition of donor erythropoiesis by residual recipient lymphocytes. A prospective randomized trial should be performed with rHuEPO starting on the day of transplantation to assess its clinical benefit in terms of transfusion requirements and quality of life

Cerebral toxoplasmosis following allogeneic hematopoietic peripheral blood stem cell transplantation with non-myeloablative conditioning

peer reviewedWe report the occurrence of a cerebral toxoplasmosis 52 days after a non-myeloablative allogeneic stem cell transplantation as treatment for acute myeloid leukemia.Nous présentons le cas d'un patient ayant hbénéficié d'une mini-allogreffe de cellules souches hématopoïétiques dusang périphérique pour une leucémie myéloïde aiguë qui développa une toxoplasmose cérébrale 52 jours après sa greffe

What Is The Role For Regulatory T-Cells After Nonmyeloablative Conditioning?

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Oral minocycline as systemic therapy for uncomplicated venous access device-related bloodstream infection with coagulase-negative staphylococci after allogeneic hematopoietic cell transplantation.

peer reviewed[en] BACKGROUND: Venous access device-related bloodstream infection (VAD-BSI) with coagulase-negative staphylococci (CoNS) is a common complication after allogeneic hematopoietic cell transplantation (alloHCT). Standard systemic antimicrobial therapy for uncomplicated VAD-BSI with methicillin-resistant CoNS consists of intravenous (IV) vancomycin (vanco). This requires hospitalization, needs new competent venous access, exposes patients to potential toxicity (mainly renal) and increases the risk of commensal flora dysbiosis with selection of vanco-resistant enterococci. Combined with VAD management (removal or antibiotic locks), oral minocycline (mino) has been evaluated as an alternative systemic therapy for the treatment of uncomplicated VAD-BSIs with CoNS at our center, primarily when the reference treatment with IV vanco was not possible (renal failure or allergy) or when hospitalization was refused by patients. Here, we retrospectively report our single center experience with this mino-based approach. PATIENTS AND METHODS: From January 2012 to December 2020, 24 uncomplicated VAD-BSIs with CoNS in 23 alloHCT patients were treated with oral mino as systemic antibiotic therapy in combination with VAD management. VAD were implantable ports (n = 17), tunneled catheter (n = 1) or PIC-lines (n = 6). Staphylococci were S. epidermidis (n = 21) or S. haemolyticus (n = 3). Mino was administered with a loading dose of 200 mg followed by 100 mg BID for 7-14 days. For 8 VAD-BSIs, patients were initially treated with IV vanco for the first 1-3 days followed by oral mino, while 16 VAD-BSIs were treated with oral mino as the sole antimicrobial agent for systemic therapy. VAD management consisted of catheter removal (for tunneled catheters and PIC-lines, n = 7) or antibiotic locks with vanco (n = 15) or gentamicin (n = 2) administered at least 3 times a week for 14 days (for ports). RESULTS: Overall, clearance of bacteremia (as assessed by negativity for the same CoNS of surveillance peripheral blood cultures drawn between day+ 3 and +30 after initiation of systemic therapy) was achieved in all but 1 patient (with port) who had persistent bacteremia at day +9. No complication such as suppurative thrombophlebitis, endocarditis, distant foci of infection or BSI-related death was observed in any patient during the 3-month period after initiation of treatment. Regarding the 17 port-BSI cases for which VAD conservative strategy was attempted, failure of 3-month VAD preservation was documented in 7/17 cases and 3-month recurrence of VAD-BSI was observed in 3/17 cases (with 1 patient with cellulitis). Treatment with mino was well tolerated except for a mild skin rash in one patient. CONCLUSION: Further prospective studies are needed to evaluate efficacy and safety of this approach

Predictors of neutralizing antibody response to BNT162b2 vaccination in allogeneic hematopoietic stem cell transplant recipients.

peer reviewedBACKGROUND: Factors affecting response to SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients remain to be elucidated. METHODS: Forty allo-HCT recipients were included in a study of immunization with BNT162b2 mRNA vaccine at days 0 and 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD) were assessed at days 0, 21, 28, and 49 while neutralizing Ab against SARS-CoV-2 wild type (NT50) were assessed at days 0 and 49. Results observed in allo-HCT patients were compared to those obtained in 40 healthy adults naive of SARS-CoV-2 infection. Flow cytometry analysis of peripheral blood cells was performed before vaccination to identify potential predictors of Ab responses. RESULTS: Three patients had detectable anti-RBD Ab before vaccination. Among the 37 SARS-CoV-2 naive patients, 20 (54%) and 32 (86%) patients had detectable anti-RBD Ab 21 days and 49 days postvaccination. Comparing anti-RBD Ab levels in allo-HCT recipients and healthy adults, we observed significantly lower anti-RBD Ab levels in allo-HCT recipients at days 21, 28 and 49. Further, 49% of allo-HCT patients versus 88% of healthy adults had detectable NT50 Ab at day 49 while allo-HCT recipients had significantly lower NT50 Ab titers than healthy adults (P = 0.0004). Ongoing moderate/severe chronic GVHD (P  0.5, P < 0.01) and more weakly with the number of follicular helper T cells (r = 0.4, P = 0.01). CONCLUSIONS: Chronic GVHD and rituximab administration in allo-HCT recipients are associated with reduced Ab responses to BNT162b2 vaccination. Immunological markers could help identify allo-HCT patients at risk of poor Ab response to mRNA vaccination. TRIAL REGISTRATION: The study was registered at clinicaltrialsregister.eu on 11 March 2021 (EudractCT # 2021-000673-83)

Contribution a l'etude des allogreffes de cellules souches hematopoietiques apres conditionnement non myeloablateur.

La maladie de greffon aiguë reste une cause importante de morbidité et de mortalité après transplantation non-myéloablative. Nous avons dans la première partie de notre travail tenté de déterminer le rôle du TNF alpha dans le développement de la GVHD aiguë en évaluant l'impact de l'élévation du TNFR-1 plasmatique des valeurs de base à J7 après transplantation sur la GVHD et sur la survie globale dans une cohorte de 106 patients ayant bénéficié d'une transplantation de cellules souches hématopoïétiques périphériques d'un donneur apparenté ou non après conditionnement non-myéloablateur. Nos données suggèrent que le conditionnement non-myéloablateur induit la production de TNF-alpha et que l'amplitude de cette production dépend de l'intensité du conditionnement (2Gy versus 4 Gy TBI). de plus, la détermination des dosages sériques du TNFR-1 avant greffe et au J7 d'une allogreffe non-myéloablative produit une information utile concernant le risque ultérieur de développer une GVHD aiguë.Dans la deuxième partie de notre travail, nous avons réalisé une étude prospective randomisée de phase 2 évaluant l'impact de la déplétion CD8 du greffon sur les résultats des transplantations non-myéloablatives. Nos observations principales ont été que la déplétion CD8 augmentait le risque de rejet de greffe, sans réduire de manière significative les incidences de GVHD aiguë de grade II-IV ou de grade III-IV. Cependant, nous avons observé une tendance non-significative vers une diminution de la GVHD aiguë de grade III-IV dans le groupe CD8-déplété (p=0.13).Enfin, dans la troisième partie de ce travail, nous avons tenté de déterminer le rôle de l'intensité du conditionnement sur l'occurence de la microangiopathie thrombotique (TMA) après transplantation allogénique. Les données provenant de 287 transplantation allogéniques réalisées entre 2000 et 2008 au CHU de Liège ont été rétrospectivement analysées. Nos données suggèrent qu'alors qu'une GVHD aiguë sévère et un donneur non-apparenté sont d'importants facteurs prédictifs de l'occurence d'une TMA, les receveurs d'une transplantation non-myéloablative ont un risque légèrement diminué de développer une TMA par rapport à ceux ayant bénéficié d'un conditionnement à hautes doses

Maladie du greffon contre l'hôte chronique : une prise en charge multidisciplinaire

peer reviewedLa maladie du greffon contre l'hôte chronique (GVHDc) est une complication fréquente des allogreffes de cellules souches hématopoïétiques. Bien que parfois considérée comme une maladie concernant uniquement l'hématologue, il s'agit en réalité d'une maladie multi-systémique qui nécessite une prise en charge pluridisciplinaire. Bien que la GVHDc soit le plus souvent modérée, les formes sévères de la maladie peuvent compromettre la qualité de vie des patients. La complication majeure de la GVHDc est l'immunodéficience secondaire qu'elle occasionne, conduisant à un risque accru de développer des infections potentiellement mortelles. Cependant, la survenue d'une GVHDc n'est pas uniquement néfaste car elle s'accompagne d'une diminution importante du risque de rechute, via l'effet de la greffe contre la tumeur. Le traitement de la GVHDc s'organise autour d'une prise en charge multidisciplinaire et comprend deux grands aspects : l'immunosuppression et les soins supportifs. Le médecin généraliste a un rôle important en ce qui concerne l'éducation du patient, le suivi, et l'accompagnement de celui-ci.Chronic Graft-Versus-Host-Disease (GVHD) is a frequent complication of allogeneic hematopoietic cell transplantation. This review article describes recent advances in the classification and treatment of chronic GVHD

Allogreffe de cellules souches hématopoïétiques chez le patient âgé : jusqu'à quel âge ?

peer reviewedEn quelques décennies, la limite d’âge pour réaliser une allogreffe de cellules souches hématopoïétiques est passée de 50-60 ans à 70-75 ans, ceci notamment grâce au développement de nouvelles procédures d’allogreffe après un conditionnement atténué ou non myéloablateur. Cet article décrit les défis et les perspectives des allogreffes chez les patients âgés.In the last decades, the upper age limit for allogeneic hematopoietic cell transplantation has increased from 50-60 years to 70-75 years of age, in part due to the development of allogeneic transplantation following reducedintensity or truly nonmyeloablative conditioning. This review describes challenges and opportunities of allogeneic hematopoietic cell transplantation in the elderly