Various kinds of late complication after hematopoietic cell transplantation (HCT) in children have been reported. These late complications are caused by preconditioning consisting of total body irradiation (TBI) and high-dose chemotherapy and/or chronic graft-versus-host disease (GVHD). The impact of late complications is serious, especially in infants/toddlers, even if the preconditioning does not involve TBI. We have to take into account that HCT in children has impacts on their growth, and such problems need to be addressed. This represents an important theme for follow-up and support of children going through education, employment, marriage and so on. In addition, we have to make efforts to develop strategies to reduce or avoid late complications.
An increasing number of cancer survivors has overcome cancer with the development of treatments for cancers of children, adolescents, and young adults. On the other hand, the impairment of function caused by cancer treatment has become a problem. In the clinical guidelines for fertility preservation in children, adolescents, and young adult cancer patients published by the Japan Society of Clinical Oncology in 2017, it is noted that cancer treatment is the top priority, but the patient should, as much as possible, be referred to see a doctor who specializes in reproductive medicine when the patient desires to have a child in the future. Myeloablative pretreatment for hematopoietic cell transplantation causes ovarian failure at a high rate. Doctors should understand their impact on fertility and how to preserve fertility and should strive to improve the quality of life of patients after hematopoietic cell transplantation by understanding and using the local oncofertility network.
Monoclonal antibodies blocking the immune checkpoints such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) on T cells enhance anti-tumor immunity and are employed in the treatment of various malignant tumors, including relapsed/refractory classical Hodgkin’s lymphoma (cHL). Though immune checkpoint blockade in the context of allogeneic hematopoietic stem cell transplantation (allo-SCT) could potentiate donor anti-tumor responses, it possibly develops severe graft-versus-host disease (GVHD) as well. In preclinical mouse models, the blockade of both CTLA-4 and PD-1 after allo-SCT develops severe GVHD. In a clinical setting, allo-SCT in patients with prior history of anti-PD-1 treatment leads to acute GVHD and a non-infectious febrile syndrome that requires the use of corticosteroids. Because the administration of PD-1 inhibitors after allo-SCT also leads to acute GVHD, it is recommended that PD-1 inhibitors should be started at a low dose against relapsed cHL post-allo-SCT. In this review, recent advances in understanding of the immunological effects and clinical outcomes of checkpoint blockade in the context of allo-SCT are summarized. Moreover, monitoring of anti-PD-1 monoclonal antibodies on T cells that could estimate the effects of PD-1 inhibitors are also discussed.
Human leukocyte antigen (HLA) -haploidentical stem cell transplantation (haplo-SCT) has been shown to be associated with a higher risk of early transplant-related mortality. This is because of complications in severe graft-versus-host disease arising due to allogeneic immune reactions and graft rejection. Therefore, traditionally, SCT from HLA-matched donors has been recommended. Contrastingly, allogeneic immune reactions induce a strong graft-versus-leukemia effect; thus, haplo-SCT is the treatment of choice for patients with relapsed/refractory leukemia. With recent advances in treatment methods, the survival rate in pediatric acute leukemia has improved. However, the prognosis of patients diagnosed with post-transplant relapsed/refractory leukemia or other relapsed diseases with poor prognostic factors continues to be dismal. We retrospectively analyzed 39 patients with relapsed/refractory acute leukemia who underwent T-cell-replete haplo-SCT between 2009 and 2016. The 3-year overall and disease-free survival rates were found to be 45.1±8.5% and 33.8±7.9%, respectively. Although these results are derived from case studies performed in a single institution, they will be important in evaluating the efficacy of prospective multi-center trials of T-cell-replete haplo-SCT.
Aprepitant is often used as an antiemetic during pretreatment for hematopoietic stem cell transplantation. However, while the patient is still under the influence of aprepitant, tacrolimus is administered from day −1 of the transplant. Aprepitant has cytochrome P450 3A4 (CYP3A4)-inhibitory activities, and tacrolimus is a substrate of CYP3A4. Therefore, the effect of aprepitant on the concentration of tacrolimus metabolized by CYP3A4 poses a concern. Our study subjects were divided into two groups as follows: The first group received aprepitant pretreatment prior to transplantation (n=25), and the second group did not (n=32). We compared the concentration/dose (C/D) ratios of tacrolimus from day 0 to day 4 post transplantation. The tacrolimus C/D ratios on transplantation day 0 of patients with (administrated until day−1) and without aprepitant administration were 553±161 and 414±138 ng・kg/mL・mg, respectively. The tacrolimus C/D ratio was significantly higher in patients who were administered aprepitant than those who were not. The pharmacodynamic effect of aprepitant on tacrolimus was particularly noticeable for one day after the completion of aprepitant administration; therefore, the evaluation of monitoring tacrolimus blood concentration was suggested important.
Various anti-cancer drugs are used in conditioning regimens for hematopoietic stem cell transplantation. Anti-cancer drugs have been reported to cause chemotherapy-induced erythema. Hand-foot syndrome (HFS) is a typical skin disorder caused by anti-cancer drugs. We conducted a retrospective investigation in our institution regarding HFS onset. We evaluated the records of 151 patients who underwent allogeneic hematopoietic stem cell transplantation in our institution from January 1, 2011 to December 31, 2015. We investigated HFS occurrence from the start of the conditioning regimen to the myelosuppression stage after transplantation using medical and nursing records. HFS occurred in 90 (59.6%) patients. The incidence of HSF was significantly lower with fludarabine/melphalan than with total body irradiation 12 Gy or with fludarabine/busulfan. Our findings suggest that the best self-care and nursing support should be considered for patients receiving each of these conditioning regimens.
Hematopoietic stem cell transplantation (HCT) recipients should be accommodated for at least 2-3 weeks in a protective environment with high-efficiency particulate air (HEPA) filters. Amenity is very important for the recipients who have to overcome hard condition, and comfortability during transplantation highly depends on equipment of isolated rooms. To minimize the inconvenience of recipients, several elaborating equipment is required, however, detailed information for design drawing of isolated rooms is rarely available. Thus, to newly establish two units of isolated rooms in our hospital, we visited four institutions and conducted an interview with staffs and patients/parents, for satisfied/dissatisfied points of the isolated rooms of each hospital. Based on the collected information, we established isolated rooms “kind-hearted” for both patients and medical staffs. We here share our design drawings for the isolated rooms with multiple ingenuity, which could contribute for basic information to newly establish isolation rooms.