FDG-PET/CT has been widely used not only at the time of diagnosis of non-Hodgkin’s lymphoma but also during and after treatment. With the help of large amount of data on Hodgkin’s lymphoma, for which FDG-PET is extraordinarily useful, evidence is also rapidly accumulating for non-Hodgkin’s lymphoma. Currently, there is a consensus that FDG-PET/CT is effective in stratifying the prognosis of non-Hodgkin’s lymphoma in a PET-avid disease, especially diffuse large B-cell lymphoma (DLBCL). However, in the enormous evidence accumulated till date, the variability in the clinical conditions of the patients, timing, and the FDG-PET/CT assessment method makes it difficult to overlook and understand the complete picture. In this article, we will review the position of FDG-PET/CT in the response assessment of DLBCL, evolution of evaluation methods, and evidence for determining therapeutic efficacy using FDG-PET/CT and for modifying treatment based on the FDG-PET/CT results.

Epigenetics is the study that involves understanding of the DNA sequence-independent mechanism of transcriptional regulation. The epigenetic regulation of gene expression is exerted via the alteration of chromatin structures through covalent modifications of core histone tails and methylation of CpG dinucleotides. In general, histone acetylation and DNA methylation are associated with transcriptional activation and repression, respectively. Histone methylation offers an additional layer for transcriptional regulation. Epigenetic abnormalities underlie the development of various hematological malignancies; for example, recurrent mutations of the DNA methyltransferase DNMT3A or DNA demethylase TET2 transform hematopoietic stem cells into preleukemic stem cells. Consequently, preleukemic stem cells give rise to T-cell lymphomas, such as angioimmunoblastic T-cell lymphoma and T-cell lymphoblastic lymphoma. Epigenetic alterations could be ideal therapeutic targets; indeed, HDAC inhibitors and DNA demethylating agents have already been used for the treatment of peripheral T-cell lymphomas. It is anticipated that more number of epigenetic drugs would be developed for clinical application in the near future.

Various treatments have been used to treat chronic immune thrombocytopenic purpura in children; however, none of it has been established as the standard of care. The administration of thrombopoietin receptor agonists (TPO-RAs) has been approved as a new treatment option in Japan. In this case series, TPO-RAs were administered to 16 patients (eltrombopag, n=9; romiplostim, n=7). Excluding the data of two patients who underwent splenectomy immediately after starting treatment with these medicines, platelet counts increased to ≥50,000/µl in seven patients. The adverse events recorded were grade 2 liver dysfunction (n=1), according to the common terminology criteria for adverse events version 4, and myelofibrosis (classified as MF1 or mild reticulin fibrosis), as observed on bone marrow biopsy (n=2). We continued the administration of TPO-RAs at the same dose in these patients because the complications they experienced were mild. The risk of adverse events associated with long-term use of TPO-RAs in this pediatric population remains unclear, and a prospective evaluation is needed.

We interviewed the adult and pediatric hematologists in the Chugoku and Shikoku regions in order to determine their opinions and attitudes about fertility preservation in 2020. A questionnaire on fertility preservation practices was sent to 59 doctors in 46 adult and pediatric hematology-oncology hospitals, out of which 52 doctors (88.1%) responded. Forty doctors (76.9%) had no rules about the explanation and 37 doctors (71.2%) answered that the attending physicians provided the explanation alone in their hospitals. Many doctors had no rules about the target age group of patients. Only few hospitals were able to complete the treatment of hematological malignancies and fertility preservation within their own infrastructure. Several doctors referred to neighboring hospitals for fertility preservation; however, five hospitals were unable to provide fertility preservation and had no relationship with other hospitals. Doctors should give fertility preservation options to all patients at risk of infertility because of their cancer treatment. It is suggested that the local networks should be utilized and relationships with neighboring hospitals strengthened.

A 77-year-old man diagnosed with mixed-phenotype acute leukemia (MPAL (B/Myeloid), NOS) achieved complete remission (CR) after eight courses of hyper-CVAD/MA therapy. However, 6 months later, blasts were observed on peripheral blood smear, and bone marrow aspiration revealed that the disease had relapsed as B lymphoblastic leukemia (ALL). At this time, he had left pleural effusion. He received two courses of inotuzumab ozogamicin (InO) and achieved second hematological CR, but the left pleural effusion worsened over time, suggesting poor disease control. After changing the regimen to blinatumomab, aspiration biopsy cytology showed that the blasts in the pleural fluid disappeared and respiratory distress improved after one course of treatment. Flow cytometry results showed increased populations of CD3-positive T-cells, suggesting that blinatumomab may have migrated into the pleural fluid and exerted an antitumor effect. Although new ALL-specific antibody drugs, such as InO and blinatumomab, are expected to improve prognosis, only few reports have described their tissue migration. The difference between InO and blinatumomab in terms of efficacy of treating malignant pleural effusion remains unclear and should be explored in additional cases.

A 69-year-old man was diagnosed with diffuse large B-cell lymphoma (DLBCL) negative for Epstein-Barr virus-encoded small nuclear RNA 1 (EBER-1) in October 2011, when he was also diagnosed as having a human T-cell leukemia virus type-I (HTLV-1) carrier. He achieved complete response after six courses of R-CHOP therapy. In February 2015, the patient had high fever and markedly elevated serum lactate dehydrogenase (LDH) level. Bone marrow examination revealed infiltration of CD4-positive T-cell malignancy. Based on the tentative diagnosis of adult T-cell leukemia/lymphoma, modified LSG15 therapy was initiated. His symptoms and serum LDH level quickly improved after the start of treatment. During the treatment, HTLV-1 proviral DNA integration was reported negative, allowing his final diagnosis to be peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Despite discontinuation of chemotherapy in the middle of the second course due to the patient’s preference, complete remission was reached. He remains in clinical remission at 28 months after the treatment discontinuation. Discordant lymphoma of DLBCL and PTCL-NOS in HTLV-1 carrier has not been well characterized and will be discussed with a literature review.

A 50-year-old man demonstrated markedly increased number of white blood cells, anemia, severe splenomegaly, and bleeding tendency. Bone marrow analysis revealed remarkable hypercellularity; dysplasia in multilineage cells, including megakaryocytes; and fibrosis. He was eventually diagnosed with triple-negative myelofibrosis. A massive hematoma developed at the bone marrow biopsy site. A similar episode recurred after the second bone marrow biopsy. The von Willebrand factor and other coagulation factor activities were within normal ranges. Platelet aggregation analyses demonstrated highly impaired aggregation induced by ADP, collagen, and epinephrine. Treatment with hydroxyurea and ruxolitinib, a JAK inhibitor, was ineffective, and he eventually died on day 144 after hospitalization. Acquired platelet dysfunction uncommonly occurs in patients with myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), without precise elucidation of the frequency and underlying mechanism. The onset of bleeding tendency in the current patient suggested that platelet dysfunction may be caused by somatic genetic events. Here, we discuss the mechanisms of acquired platelet dysfunction in MDS or MPN with a literature review.

Dysprothrombinemia is the rarest inherited bleeding disorder that is characterized by a decrease in the prothrombin activity, but normal antigen levels. In this study, we report the case of a compound heterozygote of two mutations in prothrombin; Met337Thr and Arg388His, which has previously been identified as “Prothrombin Himi.” A systemic blood coagulation evaluation revealed a prolonged prothrombin time (39%) and activated partial thromboplastin (64.4 sec), with an isolated severe decrease in the prothrombin activity (8.6%). Preoperative replacement of prothrombin with prothrombin complex concentrate, PPSB-HT “Nichiyaku,” successfully prevented abnormal postoperative bleeding after laparoscopic hysterectomy for cervical cancer. This is the second reported case of Prothrombin Himi.