With developments of flow cytometry (FCM) for detecting cells with leukemia-associated phenotypes and of polymerase chain reactions to detect leukemia specific DNA or chimeric mRNA, it has become possible to detect leukemic cells with sensitivity of 10-5 in many adult patients with Philadelphia-chromosome (Ph) -negative acute lymphoblastic leukemia. A state in which leukemic cells are not detected by such a highly sensitive method is called immunophenotypic, or molecular complete remission (CR). A leukemic burden that exists between hematological CR and immunophenotypic/molecular CR is called minimal residual disease (MRD). The significance of MRD varies depending on therapy protocol used, time points, and measurement methods.
MRD response during chemotherapy is the strongest overall prognostic indicator in adult Ph (−) ALL patients.
Post-induction MRD-negative patients have been identified to have good prognosis with chemotherapies, not suitable for up-front allogeneic hematopoietic stem cell transplantation.
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell lymphoma with a dismal prognosis and is causally associated with human T-cell leukemia virus type 1. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective treatment for patients with ATLL and can provide a chance of long-term remission through a graft-versus-ATLL effect. However, the incidence of relapse after allo-HSCT remains high at approximately 40%. Accumulating evidence shows that administering mogamulizumab and lenalidomide to patients with ATLL before or after allo-HSCT has drawbacks and advantages. Recent genomic and transcriptomic studies have shown that ATLL cells evade immune surveillance through mutated or hypermethylated genes encoding immune components and a novel regulatory mechanism of programmed death-ligand 1 (PD-L1) expression by PD-L1 3′-untranslated region disruption. Therefore, to overcome the poor prognosis of ATLL, further experimental and clinical research may lead to more effective and less toxic treatments before and after allo-HSCT. Research on immune-based therapies, such as vaccine and cell therapies against Tax or NY-ESO-1, is ongoing in Japan.
Outcomes of HLA haplo-identical transplantation using post-transplantation cyclophosphamide (PT/Cy-haplo) are similar to those of HLA-matched related/unrelated transplantation. Unlike classical HLA haplo-identical transplantation, PT/Cy-haplo does not require expensive T-cell depletion. Furthermore, accumulating evidences, including meta-analysis data, have indicated that PT/Cy-haplo may have a significant advantage over HLA-matched transplantation, concerning the low incidence of clinically significant, moderate-to-severe chronic graft-versus-host disease. This clinical advantage of PT/Cy-haplo could contribute to economic medical benefits by reducing the cost and improve the quality of life of the patients. The establishment of PT/Cy-haplo could necessitate the recalibration of the donor selection algorithm.
In patients receiving hematopoietic stem cell transplantation (HSCT), antimicrobial prophylaxis is performed to prevent severe infection and improve prognosis. However, this prophylactic measure is associated with the disruption of the intestinal microflora and the onset and deterioration of graft-versus-host disease after HSCT. A trilogy of studies published in Science in 2018 showed that the immunological effect of treatment with anti-programmed death-1 (anti-PD-1) antibody in tumor-bearing mice varied with respect to the intestinal microbiota. Moreover, they demonstrated that the anti-tumor effect exerted by treatment with the anti-PD-1 antibody was enhanced as a result of the inoculation of intestinal bacterial flora. However, the bacteria which promoted the immunotherapeutic effect were not unique to this trilogy of studies. Further, these studies failed to identify universal bacteria that are responsible for the improvement of immunotherapy. Therefore, the fecal transplantation of intestinal bacterial flora, derived from a healthy donor, was investigated and established. However, one should note that an important aspect of fecal transplantation is the restoration of favorable functioning of gut microbiota.
Graft-versus-host disease (GVHD) is one of the major complications and the leading cause of morbidity, mortality, and impaired quality of life after allogeneic hematopoietic stem cell transplantation (allo HSCT). Sequential phases of natural immunity and acquired immunity appear to form the pathological basis of GVHD. Studies have also demonstrated the important role of immune-modulatory cells in tolerance induction after allo HSCT. In this review, we focus on invariant natural killer T cells (iNKT cells), which are a unique subset of immune-modulatory cells that link natural immunity and acquired immunity, in the context of allo HSCT.
A medical device, “episil® Oral Liquid” (Japanese manufacturer: Solasia Pharma K. K., Tokyo, Japan), which protects the wound area of oral mucositis and relieves the pain of mucositis, was approved for inclusion in the Japanese national reimbursement pricing list in April 2018. However, the efficacy of and the feeling of use of episil® have not yet been investigated in Japan. Therefore, we conducted a case study in four patients who received hematopoietic stem cell transplantation (HSCT) at our hospital and experienced pain due to oral mucositis. At 5 minutes after an application of episil®, the oral pain scores decreased in three of the four patients, and it remained at the decreased level for 30 to 120 minutes thereafter. Two patients complained of a slight change in taste and a slight sensation of irritation, and one patient complained of a slight feeling of discomfort; however, all patients requested to continue using episil® at the completion of the pain assessment 2 hours after the application. No adverse event or adverse device deficiency was observed. These cases suggested that episil® Oral Liquid relieves the pain and discomfort of oral mucositis in patients who have received HSCT.
Introduction: Hematopoietic cell transplantation (HCT) is a sole curative treatment for patients with X-linked hyper IgM syndrome (XHIM), however optimal conditioning regimen has not been established. We evaluated the efficacy of HCT with reduced intensity conditioning consisting of fludarabine (Flu) and busulfan (BU) (FluBU) for XHIM. Methods: Cases were 3 boys aged 2-6 with XHIM. All cases had no complications at the time of HCT. Case 1 had already received HCT before this study. Conditioning regimen of Flu 180 mg/m2 and BU 16 doses (target AUC 60 mg*hour/L) was used in all cases. Cases 1 and 3 received rabbit anti-thymocyte globulin. Umbilical cord blood in two cases and bone marrow in one case were transplanted. Results: Engraftment and donor-type chimerism (>90%) were achieved in all cases. Cases 1 and 3 showed viral infections and hemophagocytic lymphohistiocytosis. Case 3 suffered from autoimmune cytopenia and developed secondary graft failure. Conclusions: HCT with FluBU could be feasible for patients with XHIM. However, further improvements and prophylaxis are necessary to reduce post-transplant complications.