NK cell receptor (NKR)-expressing cells have cytolytic activity against leukemic cells, while solid tumor cells escape from T cell recognition because of the low expression level of HLA class I molecules in both allogenic and autologous settings. This characteristic nature of NK cells, recognition of target cells in contrast with T cells, provides a strategy to overcome tolerance in the tumor-bearing host. Furthermore, donor alloreactive NK cells, which are induced by killer cell immunoglobulin-like receptor (KIR) ligand incompatibility between donor and recipient HLA class I in the graft-versus-host (GVH) direction, can attack leukemic cells and host antigen-presenting cells (APC), resulting in the enhancement of graft-versus-leukemia (GVL) effect and the suppression of graft-versus-host disease (GVHD) at the same time. Therefore, NK cells may play an important role on the regulation of GVHD and GVL. In addition, NK cell therapy may be a promising treatment against leukemia and solid cancers which escape from T cell immune surveillance.
To date, a variety of HLA-mismatched (haploidentical, haplo) stem cell transplantation regimens have been reported. The three most common regimens outside of Japan involve 1) ex vivo T cell depletion, 2) high dose anti-thymocyte globulin, and 3) post-transplant cyclophosphamide. According to reports, GVHD is sufficiently controlled, and each regimen could be considered a standard therapy. The magnitude of graft-versus leukemia/lymphoma (GVL) effect in each haplo regimen, however, remains unclear. All of these three regimens are generally used to target patients in complete remission (CR), In Japan, on the other hand, haplo transplants tend to be used for patients not achieving CR or in post-transplant relapse. In the haplo regimen employed at our institute, we have utilized chemokine blockage with steroid-containing GVHD prophylaxis. There are many opportunities to test various GVHD therapies for severe GVHD in haplo transplantation. In this review, I will discuss our experience with thymoglobulin, mycophenolate mofetil, infliximab, oral beclomethasone dipropionate, and mesenchymal stem cells M.
We analyzed distress associated with a prolonged hospital stay in 21 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), using the Hospital Anxiety and Depression Scale (HADS). Levels of depression and anxiety before and 90 days after transplantation were measured in the 21 patients and changes during the study period were compared between 10 of the patients, who were scheduled for discharge (discharge group), and the remaining 11 patients, who were expecting a prolonged hospital stay (prolonged hospitalization group) 90 days after transplantation, using unpaired t-test. Changes in the levels of depression and anxiety during that period in patients in the discharge group compared with those in the prolonged hospitalization group were as follows: HADS total score, －1.5±2.4 vs. 3.6± 5.2 (P＜0.05); anxiety score, －1.3 ±1.6 vs. 0.18±3.0 (P＞0.05); depression score, －0.2 ±2.7 vs. 3.5±3.6 (P＜0.05). Our results suggest that a prolonged hospital stay can statistically relate to an increase in transplant patients’ distress.
Tacrolimus has been widely used for the prophylaxis and treatment of graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation. Since tacrolimus is mainly metabolized by cytochrome P450 (CYP) enzymes, its drug interaction with a variety of agents has been clinically recognized. In addition, natural products such as food components and herbal products have also been reported to interact with tacrolimus. We here report the first case of a drug interaction between tacrolimus and rooibos tea documented after allogeneic hematopoietic stem cell transplantation, in which the interaction reduced the concentration of tacrolimus and resulted in the development of GVHD. Transplant physicians and pharmacists should be made aware of the drug-herbal interaction between rooibos tea and tacrolimus, which is probably applicable to other drugs metabolized by CYP enzymes, such as cyclosporine A.
A 58-year-old man was diagnosed with acute megakaryocytic leukemia and subsequently underwent reduced intensity allogeneic stem cell transplantation from his sibling donor. On day 6 after the transplantation, he developed febrile neutropenia, and intravenous doripenem was started. Since gram-positive rods were isolated from blood cultures, and because Bacillus cereus (B. cereus) was suspected, vancomycin therapy was added. On day 8, he developed a decreased level of consciousness and left hemiplegia. Magnetic resonance imaging of the brain revealed meningitis, multiple brain hemorrhages, and subdural hemorrhage. Bacteria from blood cultures were identified as B. cereus, and we considered that those brain lesions were caused by inflammation and septic embolism by B. cereus. On day 8, antibiotic therapy was changed to levofloxacin and imipenem/cilastatin, according to the result of antimicrobial susceptibility testing, and sepsis resolved; however, hemiplegia persisted. Since B. cereus sepsis is associated with an aggressive clinical course, especially in the context of neutropenia, effective treatment for B. cereus should be started as soon as grampositive rod bacteremia is identified.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment option to cure chronic granulomatous disease (CGD), although the selection of an alternative donor for patients with mismatched sibling donors and the role of conditioning regimens in patients with severe complications remain controversial. Here we report the clinical course of four patients with CGD who underwent HSCT in our hospital. Patient 1 underwent transplantation from an HLA-locus mismatched related donor, with a myeloablative conditioning regimen including total body irradiation (TBI). Engraftment was rapid, but he developed a second malignancy 5 years after HSCT and succumbed. Patients 2 and 3 underwent transplantation from HLA-matched sibling donors (MSD), with reduced-intensity conditioning (RIC) including low-dose TBI; engraftment was rapid. Patient 4 had severe complications and underwent transplantation from an alternative donor, with RIC including low-dose TBI. However, he died of sepsis before achieving engraftment. If matched sibling donors are available, RIC including low-dose TBI can provide stable engraftment. However, an optimal conditioning regimen for patients without MSD or those with severe complications remains unclear. Further studies are necessary to clarify these issues.