[Ovarian hyperstimulation syndrome with controlled ovarian stimulation after induction therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia].

A 27-year-old woman with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia received induction therapy with dasatinib and prednisolone. From the time of diagnosis, oocyte storage was planned in accordance with the patient's wishes. After progesterone administration for suppression of menstruation, and blood cell recovery, ovarian stimulation was performed and a sufficient number of eggs was collected. The patient was considered at high risk for ovarian stimulation syndrome (OHSS) and received cabergoline and letrozole. However, ovarian enlargement and ascites were observed on ultrasonography 2 days after egg collection, and a diagnosis of moderate OHSS was made. Circulatory management was performed and low-molecular-weight heparin was administered. Dasatinib was discontinued due to the appearance of pleural effusion. Fluid retention improved after menstruation resumed, and the patient was able to continue consolidation with dasatinib and cord blood transplantation. Although tyrosine kinase inhibitors are expected to simplify planning of oocyte storage, the risk of complicating OHSS should be noted.

Gilteritinib Affects the Selection of Dominant Clones in Clonal Hematopoiesis: Sequential Genetic Analysis of an FLT3-ITD Positive AML Patient with Long-Term Gilteritinib Therapy.

We performed sequential molecular analyses of a 75-year-old woman with de novo FLT3-ITD positive acute myeloid leukemia (AML) who had received gilteritinib therapy for 43 months. At the time of diagnosis, her karyotype was normal; however, FLT3-ITD, NPM1, DNMT3A, and IDH2 mutations were detected. She received induction therapy with daunorubicin and cytarabine and achieved hematological complete remission (HCR). After attaining HCR, she underwent consolidation therapy with azacytidine or cytarabine, aclarubicin, and granulocyte-colony stimulating factor. However, AML relapsed eight months after the first HCR. FLT3-ITD and NPM1 mutations were persistently positive, and the patient received gilteritinib therapy. Although the FLT3-ITD clone was not detected during gilteritinib treatment, a clone harboring monosomy 7 and CBL mutations emerged. Bone marrow examinations at 15, 24, and 32 months after gilteritinib treatment revealed multi-lineage blood cell dysplasia without an increase in myeloblasts. After 33 months of treatment, gilteritinib was discontinued for two months because to ileus development, and the FLT3-ITD clone was detected again. Gilteritinib treatment was restarted, and FLT3-ITD became negative. Our analysis demonstrated that: (1) hematopoiesis derived from gilteritinib-resistant clones was generated by long-term gilteritinib treatment, and (2) FLT3-ITD clones regained clonal dominance in the absence of FLT3 inhibition. These findings suggest that gilteritinib affects the selection of dominant clones during clonal hematopoiesis.

Tyrosine Kinase Inhibitors Do Not Promote a Decrease in SARS-CoV-2 Anti-Spike IgG after BNT162b2 Vaccination in Chronic Myeloid Leukemia: A Prospective Observational Study.

We performed a prospective observational study of chronic myeloid leukemia (CML) patients after anti-SARS-CoV-2 BNT162b2 vaccination (VC). In total, 32 CML patients with tyrosine kinase inhibitor (TKI) therapy, 10 CML patients with treatment-free remission, and 16 healthy subjects participated in the study. From April 2021 to September 2021, all cases (median age = 58 years) were vaccinated twice. Immunoglobulin G for SARS-CoV-2 spike protein (S-IgG) was measured at three timepoints (before the first VC, 1−5 weeks after the second VC (T1), and approximately 6 months after the second VC (T2)). S-IgG was not observed before the first VC in any participant. At T1, all cases had acquired S-IgG. There were no significant differences in S-IgG levels among groups. A paired sample comparison of median S-IgG titers between T1 and T2 in all groups showed a significant reduction in T2 S-IgG titers. There were no significant differences in S-IgG levels among groups. When all patients were analyzed, those aged ≥58 years had significantly lower S-IgG levels than those aged <58 years at T1. The BNT162b2 vaccine was highly effective in CML patients with or without TKIs, and S-IgG levels were as persistent as those in healthy individuals.

[Desquamative esophagitis associated with unrelated allogeneic peripheral blood stem cell transplantation using the FBM conditioning regimen].

Desquamative esophagitis (DE) is a rare benign condition characterized by sheet-like shedding of esophageal squamous epithelial tissue. Although cases of drug-induced DE, such as those induced by direct oral anticoagulants, have been reported, cases of DE complicated with hematopoietic stem cell transplantation (HSCT) are rare. We herein report the case of a 52-year-old woman with FLT3-ITD mutation-positive acute myeloid leukemia who presented with DE immediately after HSCT. Allogeneic peripheral blood HSCT with FBM (fludarabine 180 mg/m2, busulfan 12.8 mg/m2, and melphalan 80 mg/m2) was performed during the first remission. Tacrolimus plus short-term methotrexate was planned for graft-versus-host disease prevention. Common Terminology Criteria for Adverse Events grade 3 equivalent vomiting was observed during treatment with the conditioning regimen. On day 5 after HSCT, a white band of 10 cm in length and 1 cm in width was discharged from the oral cavity during vomiting. Upper gastrointestinal endoscopy revealed mucosal detachment in the entire esophagus and the diagnosis of DE was made. DE improved on providing conservative treatment. We concluded that the mechanical pressure that developed on the esophagus due to frequent vomiting contributed to the mucosal detachment owing to regimen-related toxicity. Even in the FBM regimen, which is widely used as a conditioning regimen, caution is required to prevent DE.

Relevance of diffusion-weighted imaging with background body signal suppression for staging, prognosis, morphology, treatment response, and apparent diffusion coefficient in plasma-cell neoplasms: A single-center, retrospective study.

Accurate staging and evaluation of therapeutic effects are important in managing plasma-cell neoplasms. Diffusion-weighted imaging with body signal suppression magnetic resonance imaging (DWIBS-MRI) allows for acquisition of whole-body volumetric data without radiation exposure. This study aimed to investigate the usefulness of DWIBS-MRI in plasma-cell neoplasms. We retrospectively analyzed 29 and 8 Japanese patients with multiple myeloma and monoclonal gammopathy of undetermined significance, respectively, who underwent DWIBS-MRI. We conducted a histogram analysis of apparent diffusion coefficient values. The correlations between each histogram parameter and staging, cell maturation, prognosis, and treatment response were evaluated. We found that the apparent diffusion coefficient values in patients with monoclonal gammopathy of undetermined significance were lower than those in patients with multiple myeloma. Pretreatment apparent diffusion coefficient values of immature myeloma were lower than those of mature myeloma. Moreover, these values decreased in proportion to stage progression in Durie-Salmon classification system but showed no significant correlation with other staging systems or prognosis. Patients were stratified as responder, stable, and non-responder based on the International Myeloma Working Group criteria. The magnitude of changes in apparent diffusion coefficients differed significantly between responders and non-responders (0.154 ± 0.386 ×10-3 mm2/s vs. -0.307 ± 0.424 ×10-3 mm2/s, p = 0.003). Although its usefulness has yet to be established, DWIBS-MRI combined with apparent diffusion coefficient measurement allowed for excellent response evaluation in patients with multiple myeloma. Furthermore, apparent diffusion coefficient analysis using DWIBS-MRI may be useful in predicting cell maturation and total tumor volume.

Elevation of HHV-6 viral load mimicking HHV-6 reactivation after second umbilical cord blood transplantation in chromosomally integrated human herpesvirus-6.

Human herpesvirus-6 (HHV-6) reactivation is an important complication in patients receiving umbilical cord blood transplantation (CBT). Chromosomally integrated human herpesvirus-6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germline genome and is transmitted in a Mendelian manner. The influence of ciHHV-6 in recipients or donors in cases of CBT is unknown. We report the first case with ciHHV-6 that received CBT twice for acute lymphoblastic T-cell leukemia. HHV-6 DNA in peripheral blood leukocytes (PBLs) was examined over time through two CBTs. After the first CBT, the HHV-6 viral load was significantly reduced by conversion to PBLs derived from the first donor. During the second CBT, an increase in HHV-6 DNA in PBLs and plasma were observed. However, HHV-6 mRNA was not detected in either the sample before 2nd CBT or at the time of HHV-6 DNA elevation. It is considered that the HHV-6 DNA detected in PBLs and plasma samples might be the HHV-6 genome released due to tissue damage. This case suggests that physicians should be aware of HHV-6 DNA variability during allogeneic hematopoietic stem cell transplantation in ciHHV-6 patients.

Epstein-Barr virus-associated post-transplant lymphoproliferative disease during dasatinib treatment occurred 10 years after umbilical cord blood transplantation.

Post-transplant lymphoproliferative disease (PTLD) is defined as a lymphoma that occurs after solid-organ or hematopoietic stem-cell transplantation (HSCT), caused by immunosuppression and Epstein-Barr virus (EBV) reactivation. It is an important post-transplant complication that can be fatal. After HSCT, most PTLD occurs within 2 years. Recent evidence suggests that tyrosine kinase inhibitors (TKIs) are expected to be effective maintenance therapy after HSCT for Philadelphia chromosome-positive leukemia. However, it is unclear whether the use of TKIs might pose a risk of developing PTLD after HSCT. We present the first case of late-onset PTLD during dasatinib treatment, which occurred 10 years after umbilical cord blood transplantation (CBT). A 59-year-old man who received CBT for chronic myeloid leukemia blast phase needed long-term dasatinib therapy for molecular relapse. Ten years after CBT, he developed diffuse-large B-cell lymphoma (DLBCL). We observed chimerism of the DLBCL sample, which indicated complete donor type and EBV-DNA, and the patient was diagnosed with PTLD. Because of treatment resistance, he died 6 months after PTLD onset. Although he received no long-term administration of immunosuppressive agents, he received long-term dasatinib treatment, which suggests that prolonged dasatinib use after CBT caused EBV reactivation and led to PTLD. Our case suggests that the potential contribution of molecular-targeted agents after HSCT to the development of PTLD should be carefully considered.

Successful cord blood transplantation for myelodysplastic syndrome complicated by Mycobacterium kansasii pneumonia.

Non-tuberculous mycobacterial (NTM) disease is a rare cause of neutropenic fever in patients with hematological malignancies. There are few studies on the optimal management for such patients with NTM. We report a case of myelodysplastic syndrome (MDS) treated by umbilical cord blood transplantation (CBT) after Mycobacterium kansasii (M kansasii) pneumonia. A 38-year-old man diagnosed with MDS developed severe pneumonia during induction chemotherapy. Repeated sputum culture uncovered mycobacterium infection. Then, by the polymerase chain reaction of the bronchial lavage fluid, M kansasii infection was proven. After 140 days of anti-NTM therapy, CBT was successfully carried out and the patient recovered without recurrence of NTM infection. This case provides valuable evidence that hematopoietic stem cell transplantation is feasible after a reliable diagnosis and continuous anti-NTM therapy.

Cardiac biopsy with intracardiac echocardiographic guidance for successful diagnosis of cardiac lymphoma.

The diagnosis and appropriate treatment of cardiac lymphoma are often delayed by the difficulty in obtaining heart tissue biopsies. Intracardiac echocardiography-guided biopsy can improve the prognosis of cardiac lymphoma by decreasing postbiopsy complications and increasing biopsy quality, allowing collection of sufficient material for multilateral analysis.

Musculoskeletal pain after stopping tyrosine kinase inhibitor in patients with chronic myeloid leukemia: a questionnaire survey.

We conducted a questionnaire survey to assess the state of patients with CML after discontinuation of TKI therapy. Nine of 27 patients developed musculoskeletal pain after TKI discontinuation. One had discontinued nilotinib and eight had discontinued imatinib therapy. Median time to symptom development after discontinuation was 2 weeks. Four experienced grade 3 symptoms as per the CTCAE ver. 4.0. One had pain persisting over a period of 21 months. There was a significant difference between patients with and without symptoms as regards female gender and the probability of persistent MMR. Awareness of this withdrawal syndrome after TKI discontinuation is imperative.