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Introduction: Although a number of patients with HIV infection and hematological disease have successfully undergone allogeneic hematopoietic stem-cell transplantation (HSCT), short and long-term outcomes remain not well known. We report the largest Spanish experience treating HIV-infected adult patients with high-risk hematological malignancies with allogeneic HSCT., Methods: We retrospectively reviewed 22 HIV-positive patients who received allogeneic HSCT in five centers in Spain., Results: A total of 22 patients with high-risk hematological malignancies were transplanted between 1999 and 2018. Median age was 44 years. With a median follow-up of 65 months (8-112), overall survival and event-free survival were 46%. Nonrelapse mortality was 14% at 12 months and relapse was 24% at 24 months. Grade II-IV acute graft-versus-host disease (GVHD) rate was 44%, and moderate/severe chronic GVHD rate was 41% at 24 months. All patients received combination antiretroviral therapy. Two patients showed severe toxicity related to drug interaction with antiretroviral therapy. 68% of patients showed infectious complications with viral infections as the most frequent cause. Two patients had invasive aspergillosis and one patient presented disseminated tuberculosis. All survivors except one maintained undetectable HIV load at last follow-up after HSCT., Conclusion: Allogeneic HSCT is an effective therapy for high-risk hematological malignancies in patients with HIV infection, and long-term HIV suppression with combination antiretroviral therapy is feasible. However, drug interactions with antiretroviral agents, occurrence of GVHD, and frequent infectious complications account for a complex procedure in this population. Selected HIV-infected patients with hematologic malignancies should be considered for allo-HSCT when indicated, in experienced centers.

Despite considerable advances in our understanding of the pathophysiology of graft-versus-host disease (GVHD), its prediction remains unresolved and depends mainly on clinical data. The aim of this study is to build a predictive model based on clinical variables and cytokine gene polymorphism for predicting acute GVHD (aGVHD) and chronic GVHD (cGVHD) from the analysis of a large cohort of HLA-identical sibling donor allogeneic stem cell transplant (allo-SCT) patients. A total of 25 SNPs in 12 cytokine genes were evaluated in 509 patients. Data were analyzed using a linear regression model and the least absolute shrinkage and selection operator (LASSO). The statistical model was constructed by randomly selecting 85% of cases (training set), and the predictive ability was confirmed based on the remaining 15% of cases (test set). Models including clinical and genetic variables (CG-M) predicted severe aGVHD significantly better than models including only clinical variables (C-M) or only genetic variables (G-M). For grades 3-4 aGVHD, the correct classification rates (CCR1) were: 100% for CG-M, 88% for G-M, and 50% for C-M. On the other hand, CG-M and G-M predicted extensive cGVHD better than C-M (CCR1: 80% vs. 66.7%, respectively). A risk score was calculated based on LASSO multivariate analyses. It was able to correctly stratify patients who developed grades 3-4 aGVHD ( P < .001) and extensive cGVHD ( P < .001). The novel predictive models proposed here improve the prediction of severe GVHD after allo-SCT. This approach could facilitate personalized risk-adapted clinical management of patients undergoing allo-SCT., (© 2018 by The American Society of Hematology.)

Chimerism dynamics in bone marrow, peripheral blood (PB), and T lymphocytes (TL) has been associated with the development of various complications after allogeneic stem-cell transplantation (allo-SCT). In the present study, the usefulness of chimerism monitoring in CD25(+)-activated leukocytes (AL), together with that in bone marrow, PB, and TL, for the anticipation of complications after allo-SCT, has been analyzed in 68 patients. In AL, we observed a slower dynamics toward complete chimerism (CC) than in PB (p = 0.042), while no significant differences were found between TL and PB (p = 0.12). Complete chimerism achievement in AL at day +30 has shown to be an independent risk factor for the development of grade II-IV acute graft-versus-host disease (aGvHD; hazard ratio [95% confidence interval]: 11.9 [1.5-91.7]; p = 0.017). Moreover, among patients achieving CC in TL and AL at different time-points after SCT (n = 17/68), the incidence of grade II-IV aGvHD was significantly higher in patients who achieved CC earlier in AL (5/5) than in those who achieved CC earlier in TL (1/11; p = 0.001). Therefore, achievement of early complete donor chimerism in CD25(+) AL is a strong predictor for the development of aGvHD. Prospective analysis of chimerism in AL could improve the post-SCT management of immunosuppressive therapy in transplanted patients., (Copyright © 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

Thymidine phosphorylase (TYMP), an enzyme involved in nucleotide synthesis, has been implicated in critical biological processes such as DNA replication, protection against mutations, and tissue repair. In this work, we retrospectively evaluated the influence of a polymorphism in the TYMP gene (rs112723255; G/A) upon the outcome of 448 patients subjected to allogeneic stem cell transplantation (allo-SCT) from an human leukocyte antigen (HLA)-identical sibling donor. The TYMP genotype of patients correlated with overall survival-carriers of the minor allele (A) being at an increased risk of dying after transplantation (hazard ratio, HR = 1.9; P = 0.004). This effect was mostly due to differences in transplant toxicity-related mortality (HR = 2.5; P = 0.029). In addition, the TYMP genotype of donors was associated with the risk of chronic graft-versus-host disease (GVHD)-carriers of the minor allele being at an increased risk of developing this complication ([HR] = 1.7; P = 0.039). The impact of such polymorphism on the risk of chronic GVHD is limited to patients transplanted in early stage disease (HR = 2.2; P = 0.019). The combination of a donor harboring the minor allele with a patient homozygous for the major allele was associated with the highest risk of chronic GVHD (HR = 2.8; P = 0.008). These findings provide the first evidence of the significant impact of the TYMP genotype upon the clinical outcome of patients treated with HLA-identical sibling allo-SCT., (© 2013 Wiley Periodicals, Inc.)

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a well-established therapeutic option for hematological malignancies. Combination antiretroviral therapy (cART) has enabled the treatment of medical conditions in patients infected with the human immunodeficiency virus (HIV) in the same way as in the general population. Moreover, improvements in supportive care have allowed HIV-infected patients with life-threatening hematological disorders to be treated with Allo-HSCT. We report on four HIV-infected patients with hematological malignancies receiving an Allo-HSCT in our institution, and on the use of donor lymphocyte infusions to successfully treat post-Allo-HSCT relapse. Of note, one of them is the first HIV(+) patient to receive a "dual transplant" (unrelated umbilical cord blood stem cells combined with mobilized T cell-depleted CD34(+) stem cells from a mismatched third party donor). cART drugs interactions were satisfactorily managed. This approach provided long-term control of the hematological disease. Nevertheless, despite adequate immune reconstitution, infections were the main cause of morbidity and mortality after Allo-HSCT.

Background and Objective: Donor lymphocyte infusions (DLI) have proven to be useful for the treatment of relapse after allogenic stem cell transplantation (SCT) and for the conversion of mixed chimerism (MC) into complete chimerism. The objective of the present study is to analyze the results of DLI used in both scenarios in a single centre., Patients and Method: Twenty five patients were retrospectively analyzed: DLI was used for relapse treatment in 18 cases and for conversion of mixed chimerism in 7., Results: Six patients from the first group (35%) showed response in a median of 137 days (23-250). After a median follow-up of 12 months (7 months-8 years), 5 patients remained in complete remission. Additionally, one patient recieved prophylactic DLI with good results. Six of the 7 patients (85%) who received DLI for MC showed response. After a median follow-up of 7 years (6-8), 4 patients (57%) remained in remission., Conclusions: In our experience, DLI showed clinical benefit in the management of mixed chimerism, although it was less useful in the management of relapse. Novel strategies should be considered in high risk patients., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

Background and Objectives: Despite the great utility of chimerism analysis after allogeneic stem cell transplantation, a gold standard method for its quantification has not yet been defined. The objective of the present investigation was to compare the sensitivity (detection limit) and the quantification accuracy of fluorescent in situ hybridization with specific probes for the sex chromosomes (XY-FISH) and multiplex short tandem repeat polymerase chain reaction (STR-PCR) revealed by capillary electrophoresis for the quantification of chimerism after stem cell transplantation., Design and Methods: A first experiment was performed on two sets of artificial cell mixtures from two sex-mismatched healthy donors mixed in different proportions (% male: 100, 75, 50, 25, 10, 5, 3, 1, 0.1, 0). In a second experiment, 58 samples obtained from 10 selected patients with different clinical courses and chimerism evolution after sex-mismatched stem cell transplantation, which had been studied by XY-FISH, were retrospectively analyzed by STR-PCR. In a third experiment, 60 unselected prospective samples belonging to 15 patients (5 of whom had also been included in the retrospective study) were analyzed by both XY-FISH and STR-PCR., Results: Both techniques showed high quantification accuracy and were highly reproducible. The sensitivity of both approaches reached 1% under standard conditions. Moreover, the use of long injection times for the capillary electrophoresis (30 and 50s vs. the standard 10s) resulted in an increase of sensitivity of the STR-PCR assay up to 0.1%, which has interesting clinical implications., Interpretation and Conclusions: Considering the high sensitivity and quantification accuracy of multiplex STR-PCR and the fact that this assay is sex-independent and can be applied to virtually all patients, STR-PCR could be considered as the method of choice for chimerism quantification after stem cell transplantation when high sensitivity is not a requirement.

Increasing mixed chimerism (MC) after allogeneic stem cell transplantation (SCT) has been associated with a high risk of relapse in acute leukemia. We evaluated a new method for chimerism detection, based on the quantitative real-time PCR (qrt-PCR) amplification of null alleles or insertion/deletion polymorphisms (indels). All qrt-PCR assays with null alleles and indels attained a sensitivity of at least 10-4, as well as good intra- and interassay concordance, and a high accuracy in experiments with cell mixtures. Informativeness was found in 80.3%of the 61 donor/recipient pairs tested. Nonrelapsed patients showed a progressive decrease in peripheral blood chimerism to values below 0.01%(complete chimerism (CC)). Bone marrow chimerism failed to reach CC more than 4 years after SCT. Increasing MC was observed prior to relapse in 88.2%of patients. Compared with conventional PCR amplification of variable number of tandem repeats, qrt-PCR predicted a significantly higher number of relapses (88.2 vs 44.4%) with a median anticipation period of 58 days. In conclusion, chimerism determination by qrt-PCR amplification of null alleles and indels constitutes a useful tool for the follow-up of patients with acute leukemia after SCT, showing better results than those obtained with conventional PCR.Leukemia (2005) 19, 336-343. doi:10.1038/sj.leu.2403622 Published online 20 January 2005 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about mesemeric inflammatory veno-occlusive disease (MIVOD) after allogeneic peripheral blood stem cell transplantation (PBSCT) published in the previous issue.