scholarly journals The efficacy of the regimens of “graft versus host” disease prophylaxis after hematopoietic stem cell transplantation from unrelated donors in children: single center experience

2020 ◽  
Vol 19 (2) ◽  
pp. 71-82
Author(s):  
N. V. Sidorova ◽  
A. S. Slinin ◽  
E. B. Machneva ◽  
V. V. Konstantinova ◽  
A. E. Burya ◽  
...  

Graft versus host” disease (GvHD) is one of the most frequent and severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The optimal model of GvHD prophylaxis in allo-HSCT from alternative donors in children currently remains actual question. Materials and methods. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Healthcare of Russian Federation. Two hundred fifty six allo-HSCT were made during the period 2003–2019 from matched unrelated donors (MUD). Age median was 7.1 years old. The source of hematopoietic stem cells (HSCs) bone marrow – 76% (n = 194), peripheral blood stem cells – 24% (n = 62). GvHD prophylaxis included: tacrolimus (Tacro), cyclosporin A (CsA), methotrexate (Mtx), mycophenolate mofetil (MMF), in following combinations Tacro/Mtx (n = 98), Tacro/MMF (n = 102), tacro/Mtx + MMF (n = 3), CsA/Mtx (n = 24), CsA/Mtx + MMF (n = 12), CsA + MMF (n = 14). Median follow-up 8.9 years. GvHD prophylaxis regimen did not affect significantly the toxicity of therapy (toxicity: severe mucositis grade III–IV, nephrotoxicity, hepatotoxicity) (p = 0.4; p = 0.24; p = 0.62 respectively). In our study the rate of the overall survival (ОS) has significant differences in depending of the source of prevention GvHD. The using a combination of tacrolimus and cyclosporine with low doses of methotrexate had a positive effect on OS (p = 0.035) in patients of common non-malignant and malignant groups, as well as on the level of 2-year relapse-free survival in the group of children with malignant disorders (p = 0.671). In the general group the OS the worst results were achieved when MMF was included in the prophylaxis model. In this experience of treating of a large cohort of patients the choice of calcineurin inhibitors and methotrexate as the agent GvHD prophylaxis showed the efficacy and safety for non-manipulated MUD for both malignant and non-malignant diseases in children.

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 490-500 ◽  
Author(s):  
Francisco M. Marty ◽  
Julie Bryar ◽  
Sarah K. Browne ◽  
Talya Schwarzberg ◽  
Vincent T. Ho ◽  
...  

AbstractSirolimus-based immunosuppressive regimens in organ transplantation have been associated with a lower than expected incidence of cytomegalovirus (CMV) disease. Whether sirolimus has a similar effect on CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT) is not known. We evaluated 606 patients who underwent HSCT between April 2000 and June 2004 to identify risk factors for CMV reactivation 100 days after transplantation. The cohort included 252 patients who received sirolimus-tacrolimus for graft-versus-host disease (GVHD) prophylaxis; the rest received non–sirolimus-based regimens. An initial positive CMV DNA hybrid capture assay was observed in 225 patients (37.1%) at a median 39 days after HSCT for an incidence rate of 0.50 cases/100 patient-days (95% confidence interval [CI], 0.44-0.57). Multivariable Cox modeling adjusting for CMV donor-recipient serostatus pairs, incident acute GVHD, as well as other important covariates, confirmed a significant reduction in CMV reactivation associated with sirolimus-tacrolimus–based GVHD prophylaxis, with an adjusted HR of 0.46 (95% CI, 0.27-0.78; P = .004). The adjusted HR was 0.22 (95% CI, 0.09-0.55; P = .001) when persistent CMV viremia was modeled. Tacrolimus use without sirolimus was not significantly protective in either model (adjusted HR, 0.66; P = .14 and P = .35, respectively). The protective effect of sirolimus-containing GVHD prophylaxis regimens on CMV reactivation should be confirmed in randomized trials.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Mohammad Faizan Zahid ◽  
David Alan Rizzieri

Despite the advent of targeted therapies and novel agents, allogeneic hematopoietic stem cell transplantation remains the only curative modality in the management of hematologic disorders. The necessity to find an HLA-matched related donor is a major obstacle that compromises the widespread application and development of this field. Matched unrelated donors and umbilical cord blood have emerged as alternative sources of donor stem cells; however, the cost of maintaining donor registries and cord blood banks is very high and even impractical in developing countries. Almost every patient has an HLA haploidentical relative in the family, meaning that haploidentical donors are potential sources of stem cells, especially in situations where cord blood or matched unrelated donors are not easily available. Due to the high rates of graft failure and graft-versus-host disease, haploidentical transplant was not considered a feasible option up until the late 20th century, when strategies such as “megadose stem cell infusions” and posttransplantation immunosuppression with cyclophosphamide showed the ability to overcome the HLA disparity barrier and significantly improve the rates of engraftment and reduce the incidence and severity of graft-versus-host disease. Newer technologies of graft manipulation have also yielded the same effects in addition to preserving the antileukemic cells in the donor graft.


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