Successful treatment of a pure red cell aplasia patient following ABO-mismatched hematopoietic stem cell transplantation from a sibling donor with multiple sclerosis.

Despite the importance of blood group compatibility in solid organ transplantation, the role of ABO antigens is less critical in hematopoietic stem cell transplantation (HSCT). However, ABO-mismatch HSCT can present specific conditions and challenges for the recipient. One of the possible consequences of ABO-mismatch HSCT is pure red cell aplasia (PRCA). Although there are different treatment strategies to manage PRCA, each may carry its own risk. Here, we report a patient who developed PRCA after ABO-mismatch allogeneic HSCT from her sibling with multiple sclerosis history. PRCA improved with tapering immunosuppressive agents. Although the patient developed manageable graft versus host disease (GVHD), she eventually recovered from both PRCA and GVHD.

Post-hematopoietic stem cell transplantation relapse: Role of checkpoint inhibitors.

Background and Aims: Despite the revolutionary effects of hematopoietic stem cell transplantation (HSCT) in treating hematological malignancies, post-HSCT relapse is considered a critical concern of clinicians. Residual malignant cells employ many mechanisms to evade immune surveillance and survive to cause relapse after transplantation. One of the immune-frustrating mechanisms through which malignant cells can compromise the antitumor effects is misusing the self-limiting system of immune response by overexpressing inhibitory molecules to interact with the immune cells, leading them to so-called "exhausted" and ineffective. Introduction of these molecules, known as immune checkpoints, and blocking them was a prodigious step to decrease the relapses. Methods: Using keywords nivolumab, pembrolizumab, and ipilimumab, we investigated the literature to figure out the role of the immune checkpoints in the HSCT setting. Studies in which these agents were administrated for relapse after transplantation were reviewed. Factors such as the interval from the transplant to relapse, previous treatment history, adverse events, and the patients' outcome were extracted. Results: Here we provided a mini-review discussing the experiences of three immune checkpoints, including nivolumab, pembrolizumab, and ipilimumab, as well as the pros and cons of using their blockers in relapse control after HSCT. In conclusion, it seems that CI therapy seems effective for this population. Future investigations may provide detailed outlook of this curative options.

In-depth summary over cytomegalovirus infection in allogeneic hematopoietic stem cell transplantation recipients.

In this study, we reviewed various aspects of cytomegalovirus infection, including pathophysiology, diagnosis methods, and antiviral treatments. Background: Infections continue to be a major reason of complications like high non-relapse morbidity and mortality rate after allogenic hematopoietic stem cell transplantation. Cytomegalovirus is the most common infection in immunocompromised patients or those with graft-versus-host disease. The Latent-cytomegalovirus disease could increase the risk of reactivation in allogenic hematopoietic stem cell transplantation patients and lead to profound adverse effects on transplantation outcomes. Cytomegalovirus-specific CD4 + and CD8 + T cells reconstitution is crucial for protection against the virus reactivation. Different prophylactic, pre-emptive, and therapeutic anti-viral drugs are available to prevent cytomegalovirus infection/reactivation and treat resistant infections. Conclusion: Although there has been introduced various CMV antiviral treatment strategies like antiviral drugs, Vaccination, passive immunotherapies and adoptive transfer of CMV-specific T cells, further clinical trials are required to approve current therapies.

IFNG-AS1 and MAF4 long non-coding RNAs are upregulated in acute leukemia patients who underwent bone marrow transplantation.

PURPOSE OF THE STUDY: Acute graft versus host disease (aGVHD) is an immune-mediated reaction that results in impaired immune and body function after allogeneic hematopoietic stem cell transplantation (allo-HSCT). lncRNAs have been discovered as particular T cell regulators, and alloreactive T cells have been known as a critical factor in aGVHD. As a result, we investigated the importance of lnc-MAF4 and IFNG-AS1 expression levels in aGVHD patients versus non-aGVHD patients. MATERIAL AND METHODS: This research included 38 patients with hematological disorders who were undergoing primary allo-HSCT. Human identical siblings or unrelated donors were used to collect stem cell. Samples were taken within days 0, 7, 14, 28, and 52±8 after transplantation. The expression of lncRNA levels was measured using the QRT-PCR technique. And the data were analyzed using GraphPad Prism 6 RESULTS: Our data revealed that LncRNA MAF4 and INFG-AS1 expression levels in aGVHD were not significantly different compared to the non-GVHD group immediately after transplantation, nor at day 7 or 14. However, the aGVHD group showed an overt up-regulation of the two lncRNAs on samples taken at day 28 and 52±8 compared to non-GVHD patients. DISCUSSION: Since the intracellular pathway of these lncRNAs shows a direct relationship with the IFNγ cytokine production resulting in differentiation to TH1 cells and inhibition of differentiation to TH2 cells, they can be, therefore, considered as suitable molecular candidates for the prediction of aGVHD in patients receiving HSCT.

The apheresis content analysis in Allo-HSCT represents reliable influential factors on graft-versus-host disease and overall survival.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an established treatment for hematologic malignancies. However the post-HSCT outcome can be affected by multiple pre-transplant, transplant, and post-transplant factors. The cellular content of graft could be possible factors influencing the graft-versus-host disease (GVHD) and overall survival (OS) as transplantation outcomes. PURPOSE: The aim of this study was to assess the impact of infused CD34+ cells, CD3+ cells, and MNC count on the patients' survival and incidence of graft-versus-host disease (GVHD). MATERIAL AND METHODS: We analyzed 87 patients with hematological malignancies who underwent allogeneic hematopoietic stem cell transplantation at the Taleghani Stem Cell Transplantation and Cell therapy center, Tehran, Iran from January 2016 to December 2018. Patients were conditioned with either myeloablative conditioning regimen or reduced-intensity regimen. RESULT: A CD34+ cell dose < 4.35 × 106/kg and CD3+ cell dose < 365 × 106/kg was associated with higher survival and lower acute and chronic GVHD incidence, although their association was not statistically significant. Moreover, there was a significant association between MNC count < 6.15 × 108/kg and acute GVHD incidence. CONCLUSION: Graft cell dose, lower than the cut-off level, could lead to better outcomes after allogeneic transplantation. However, this study showed that future investigations are required in a larger population of patients in order to determine the exact effect of allogeneic graft cell dose on transplantation outcome.

Application of latent class analysis in diagnosis of graft-versus-host disease by serum markers after allogeneic haematopoietic stem cell transplantation.

Graft-versus-host disease (GVHD) is one of the major causes of morbidity and mortality in 25-70% of patients. The gold standard (GS) test to confirm the diagnosis of GVHD has some limitations. The current study was conducted to evaluate the accuracy of three serum markers in diagnosing GVHD without a GS. 94 patients who were hospitalized for allogeneic transplantation were studied. Mean levels from day of haematopoietic stem cell transplantation (HSCT) to discharge of serum uric acid (UA), lactate dehydrogenase (LDH), and creatinine (Cr) were measured for all participants. We adapted a Bayesian latent class analysis to modelling the results of each marker and combination of markers. The Sensitivity, Specificity, and area under receiver operating characteristic curve (AUC) for LDH were as 51%, 81%, and 0.70, respectively. For UA, the Sensitivity, Specificity, and AUC were 54%, 75%, and 0.71, respectively. The estimated Sensitivity, Specificity, and AUC of Cr were 72%, 94%, and 0.86, respectively. Adjusting for covariates, the combined Sensitivity, Specificity, and AUC of the optimal marker combination were 76%, 83%, and 0.94, respectively. To conclude, our findings suggested that Cr had the strongest diagnosis power for GVHD. Moreover, the classification accuracy of the three-marker combination outperforms the other combinations.

The association of conditioning regimen with cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Infections is yet one of the life-threatening complications of the hematopoietic stem cell transplantation (HSCT). The myeloablative and immunosuppressive conditioning regimens, which are administered before HSCT, dampen the defense capacity of the recipients' immune systems. In this condition, opportunistic infections, especially viral infections such as cytomegalovirus (CMV) can be reactivated and cause morbidity and mortality in HSCT patients. Here, we aimed to find out any possible relationship between types of conditioning regimen and CMV reactivation in allogeneic HSCT patients. MATERIALS AND METHODS: We retrospectively analyzed the data of 145 CMV-seropositive cases out of total 201 allo-HSCT patients, including age, gender, underlying disease, conditioning regimen, prophylaxis regimen and occurrence of acute graft-versus-host disease (aGVHD) to evaluate their roles in CMV reactivation. RESULTS: Our result showed that conditioning regimen containing Busulfan and Fludarabine (P=0.003) or Cyclophospha-mide (P=0.02) significantly decrease the early CMV reactivation. Patients who developed aGVHD (P=0.003) and those who received anti-thymocyte globulin (ATG) as prophylaxis regimen (P=0.002), had 1.84 and 2.63 times higher risks of CMV reactivation, respectively. CONCLUSION: Our findings suggest the conditioning regimen, aGVHD and ATG as influencing factors for early CMV reactivation post-HSCT which should be considered in the future studies.

Effects of ABO incompatibility on the outcome of allogeneic hematopoietic stem cell transplantation.

BACKGROUND: ABO compatibility between donor and recipient is no necessary in allogeneic hematopoietic stem cell transplantation (AHSCT). Incompatible transplantations can be divided into three groups based on the donor and recipient blood groups. The influence of each kind of incompatibilities on the outcome of patients does not seem to be consistent. This study aimed to investigate the outcome of AHSCT patients focusing on compatibility statues. METHOD: This retrospective study was conducted on 186 patients who underwent first AHSCT, includes 108 identical, 38 minor, 32 major and eight bidirectionalABO incompatible recipients. Comparative analysis was performed for common clinical transplantation outcomes. RESULTS: There was no statistically significant association betweenABO incompatibility and graft-versus-host disease, WBC or platelet engraftment, and transfusion requirement. WBC engraftment rate was significantly lower in minor-incompatible patients. Furthermore, total and direct bilirubin which (the hemolysis biomarkers) were considerably higher in the bidirectional incompatible group, compared to the other patients. CONCLUSION: Our results indicate that theABO incompatibility might be an effective factor in engraftment time and laboratory hemolysis. Elucidating the impact of ABO incompatibility on the clinical outcome of patients warrants an extended and deep investigation in a large-scale study with comprehensive variables such as survival, relapse, and other complication of transplantation.

The role of Pax5 in leukemia: diagnosis and prognosis significance.

Pax5 transcription factor, also known as B-cell specific activator protein (BSAP), plays a dual role in the hematopoietic system. Pax5 expression is essential in B-cell precursors for normal differentiation and maturation of B-cells. On the other hand, it inhibits the differentiation and progress toward other lineages. The expression of this factor is involved in several aspects of B-cell differentiation, including commitment, immunoglobulin gene rearrangement, BCR signal transduction and B-cell survival, so that the deletion or inactivating mutations of Pax5 cause cell arrest in Pro-B-cell stage. In recent years, point mutations, deletions and various rearrangements in Pax5 gene have been reported in several types of human cancers. However, no clear relationship has been found between these aberrations and disease prognosis. Specific expression of Pax5 in B-cells can raise it as a marker for the diagnosis and differentiation of B-cell leukemias and lymphomas as well as account for remission or relapse. Extensive studies on Pax5 along with other genes and immunomarkers are necessary for decisive results in this regard.