Hematopoietic stem cell transplantation (HSCT) involves some serious transplant-related complications or vascular disorders, such as graft-versus-host disease (GVHD), veno-occlusive disease (VOD), and thrombotic microangiopathy (TMA). The diagnosis of acute GVHD after HSCT remains clinical symptoms, laboratory data and tissue histology. Various candidate biomarkers for acute GVHD are reported because of a postulated role in the pathophysiology of GVHD. The biomarkers of chronic GVHD are immunological factors, because this disease often presents with clinical manifestations that resemble those observed in autoimmune diseases. VOD is also dependent on a clinical syndrome characterized by tender hepatomegaly, jaundice, fluid retention, and unexplained weight gain. When TMA is descrived in patients who have undergone HSCT, it is often implied that the clinical diagnosis of TMA is similar to that of thrombotic thrombocytopenic purpura. Therefore, level of cytokines, chemokines and soluble molecules appear to be useful biomarkers for VOD and TMA after HSCT. Further investigations need for the ultimate goals of identifying specific biomarkers for these complication after HSCT.
Hematopoietic cell transplantation for the treatment of hematological diseases is performed in approximately 5,000 patients per year in Japan. This number is gradually increasing along with the survival rate due to expanded indications for treatments and supportive therapy and the fact that transplantation is now possible in the elderly. Many studies are now underway to clarify the effects of transplant therapy not only in terms of survival and complications but also quality of life (QOL). Recovery of post-treatment QOL takes years, and many problems such as physical, social, role function, cognitive function, fatigue and economic issues are noted. Patient QOL also affects the people who support these patients. When supporting the care of such patients, it must not be forgotten that depression is 3.5 times more likely to occur in the partners of such patients than in the healthy population, and that donors might experience complex emotions including anxiety and responsibility as well as positivity with regards to the donation. Thus, support devised together with the patient that responds to the patient's needs based on a sensitive understanding of the problems they and the people supporting them face may aid such patients and those supporting them in working out how to independently solve problems.
We retrospectively evaluated the effect of blood tacrolimus concentration early after cord blood transplantation (CBT) on acute graft-versus-host disease (GVHD). Twenty-eight patients who underwent CBT and received continuous tacrolimus infusion were included. The mean concentration of tacrolimus during the second week (17.8±3.7ng/mL in 0-Ⅰ versus 12.6±3.7 in Ⅱ-Ⅳ; P<.01) after CBT was significantly associated with gradeⅡ-Ⅳ acute GVHD. On the receiver operator characteristic curves, a cutoff value of 15ng/mL during the second week, provided the best balance between sensitivity and specificity. Multivariate analysis demonstrated that a mean tacrolimus concentration<15ng/mL during the second week was a significant risk factor for gradeⅡ-Ⅳ acute GVHD (hazard ratio, 0.22; 95% confidence interval, 0.07-0.69; P<.01). Early post-CBT tacrolimus concentration has a significant impact on the development of gradeⅡ-Ⅳ acute GVHD.
A 47-year-old man with chronic myeloid leukemia (CML) progressed to blastic crisis (BC) due to poor compliance with imatinib therapy and developed a central nervous system disease during dasatinib therapy. After achieving disease control with chemotherapy, allogeneic bone marrow transplantation was performed followed by whole-brain irradiation. As the patient developed an overlap subtype of chronic graft-versus-host disease (GVHD) affecting mainly the liver and gastrointestinal tract, methylprednisolone at 1mg/kg was started on day 107. However, as the BCR-ABL mRNA level increased on day 121, the steroid dose was decreased. To control gastrointestinal GVHD, oral beclomethasone dipropionate (BDP) at 4mg/day was started on day 173. Digestive tract-related symptoms improved with BDP and the drug was gradually tapered and withdrawn on day 285. The patient has maintained an undetectable BCR-ABL mRNA level. Oral BDP successfully controls gastrointestinal GVHD without affecting systemic graft-versus-leukemia effect and is useful in patients with CML who are resistant to tyrosine kinase inhibitors.
The following is a case of a 40-year-old man who showed acute myeloid leukemia (AML) with paroxysmal nocturnal hemoglobinuria (PNH). Unrelated bone marrow transplantation using a myeloablative conditioning regimen (cyclophosphamide, 120mg/kg; total-body irradiation, 12Gy) was performed 6 years after the diagnosis of PNH. We administered eculizumab seven times, until 4 days before transplantation; hemolysis findings improved before transplantation. We observed a mild, temporary increase in LDH after transplantation, but the level was normalized after day 19, and no acute hemolytic reactions due to withdrawal of eculizumab were identified. Complete donor engraftment was observed after transplantation, and AML remained in remission. Use of allogeneic hematopoietic stem cell transplantation for PNH is the only treatment that can lead to complete recovery in patients who have developed hematopoietic deficiency and malignancy. The effects of eculizumab on allogeneic hematopoietic stem cell transplantation are unclear, but engraftment was immediately achieved and no serious graft-versus-host disease or infection occurred in this case. The utility and safety of using eculizumab with allogeneic hematopoietic stem cell transplantation needs to be determined by accumulating additional cases.