Successful treatment with mesenchymal stem cells for steroid-refractory late-onset idiopathic pneumonia syndrome following allogeneic hematopoietic cell transplantation.

The reportedly poor outcome of late-onset idiopathic pneumonia syndrome (IPS) necessitates new approaches to its treatment. A 55-year-old man who had undergone allogeneic hematopoietic cell transplantation (allo-HCT) for myelodysplastic syndrome 1 year ago developed dyspnea with acute skin graft-versus-host disease (GVHD) flare-up while tapering immunosuppressive agents. He presented with acute respiratory distress syndrome with ground-glass opacities in the right upper and left lower lobes. All infectious tests, including multiplex polymerase chain reaction of nasal wash, were negative, and broad-spectrum antibiotic therapy was refractory. The patient was diagnosed with late-onset IPS and was refractory to methylprednisolone pulse therapy. He then showed a favorable response to mesenchymal stem cell (MSC) infusion. After eight infusions of MSCs, he had no IPS recurrence for over one year. Recently, preclinical studies have reported the potential therapeutic utility of MSC infusion for treating IPS, and our case supports its potential for treating late-onset IPS.

Dynamic Relapse Prediction by Peripheral Blood WT1mRNA after Allogeneic Hematopoietic Cell Transplantation for Myeloid Neoplasms.

Although various relapse prediction models based on pretransplant information have been reported, they cannot update the predictive probability considering post-transplant patient status. Therefore, these models are not appropriate for deciding on treatment adjustment and preemptive intervention during post-transplant follow-up. A dynamic prediction model can update the predictive probability by considering the information obtained during follow-up. This study aimed to develop and assess a dynamic relapse prediction model after allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) using peripheral blood Wilms' tumor 1 messenger RNA (WT1mRNA). We retrospectively analyzed patients with AML or MDS who underwent allo-HCT at our institution. To develop dynamic models, we employed the landmarking supermodel approach, using age, refined disease risk index, conditioning intensity, and number of transplantations as pretransplant covariates and both pre- and post-transplant peripheral blood WT1mRNA levels as time-dependent covariates. Finally, we compared the predictive performances of the conventional and dynamic models by area under the time-dependent receiver operating characteristic curves. A total of 238 allo-HCT cases were included in this study. The dynamic model that considered all pretransplant WT1mRNA levels and their kinetics showed superior predictive performance compared to models that considered only pretransplant covariates or factored in both pretransplant covariates and post-transplant WT1mRNA levels without their kinetics; their time-dependent areas under the curve were 0.89, 0.73, and 0.87, respectively. The predictive probability of relapse increased gradually from approximately 90 days before relapse. Furthermore, we developed a web application to make our model user-friendly. This model facilitates real-time, highly accurate, and personalized relapse prediction at any time point after allo-HCT. This will aid decision-making during post-transplant follow-up by offering objective relapse forecasts for physicians.

Effectiveness of venetoclax and azacytidine against myeloid/natural killer cell precursor acute leukemia.

Myeloid/natural killer (NK) cell precursor acute leukemia (MNKPL) is a rare leukemia subtype that possibly originates from precursor NK cells. The disease has a poor prognosis, and information on its treatment is lacking. We herein report the first case of a 46-year-old woman with MNKPL who was refractory to two lines of acute myeloid leukemia (AML)-type intensive chemotherapy but was successfully treated with venetoclax and azacytidine (VEN/AZA). She was diagnosed with MNKPL based on the conformations of immature lymphoblastoid morphology without myeloperoxidase reactivity that showed a CD7/CD33/CD34/CD56/HLA-DR positive phenotype and extramedullary regions. The disease was refractory to induction therapy with daunorubicin and cytarabine (DNR/Ara-C) and to reinduction therapy with mitoxantrone, etoposide, and cytarabine (MEC). After two lines of induction chemotherapy, massive pericardial and pleural effusion was found, and was suspected to be extramedullary lesions. The patient developed cardiac tamponade and required pericardiocentesis. Thus, VEN/AZA was administered as third-line therapy. After two cycles of VEN/AZA, the pericardial and pleural effusion disappeared, and complete remission was achieved. The patient received post-transplant cyclophosphamide-based haploidentical transplantation and has stayed relapse-free as of her last follow-up examination 2 years after diagnosis.

Delayed immune-related neutropenia with hepatitis by pembrolizumab.

Case presentation: A 72-year-old man with non-small-cell lung cancer received four cycles of pembrolizumab-containing chemotherapy. He developed multiple immune-related adverse events (irAEs) and discontinued immune checkpoint inhibitors (ICIs); however, he developed immune-related hepatitis and grade 4 neutropenia at 92 days and 118 days, respectively, from discontinuation. He received G-CSF and methylprednisolone pulse therapy and recovered from neutropenia 12 days later. Discussion & conclusion: ICI-induced neutropenia is a life-threatening condition. The longest recorded onset in one study cohort is 26 days after the final administration of ICIs. This case developed strikingly delayed immune-related neutropenia manifesting as a delayed irAE. Clinicians should pay close attention to delayed immune-related neutropenia as a possible life-threatening irAE after ICI treatment.

Lay abstract This case report describes a 72-year-old man with non-small-cell lung cancer who received four cycles of pembrolizumab-containing chemotherapy. He developed multiple immune-related adverse events (irAEs), which are significant side effects of immune checkpoint inhibitors (ICIs). Despite the discontinuation of pembrolizumab due to multiple irAEs, he developed immune-related hepatitis and neutropenia at 92 days and 118 days, respectively, after the final pembrolizumab dose. He received supportive care and immunosuppressive therapy and recovered from neutropenia. Recently, delayed development of irAEs was reported even in patients that discontinued ICIs; this is referred to as a delayed immune-related event (DIRE). This case developed strikingly delayed immune-related neutropenia as a DIRE. Clinicians should pay close attention to neutropenia as a possible life-threatening DIRE after ICI treatment.

Successful management of therapy-related chronic myelomonocytic leukemia with cytarabine, aclarubicin, and azacitidine following tegafur/gimeracil/oteracil.

A 55-year-old man was diagnosed with therapy-related chronic myelomonocytic leukemia (t-CMML) after exposure to tegafur/gimeracil/oteracil. Although he was refractory to hydroxyurea and low-dose cytarabine, combination therapy with cytarabine, aclarubicin and azacitidine (CA-AZA) provided good disease control, and he underwent allogeneic stem cell transplantation. This report has two key massages. First, tegafur/gimeracil/oteracil may have a potential risk of developing t-CMML. Second, CA-AZA therapy may be considered as a therapeutic option for patients with t-CMML.

[Hypomagnesemia induced by gastrointestinal losses due to carfilzomib].

A 67-year-old man with multiple myeloma had been treated with carfilzomib, lenalidomide, and dexamethasone (KRd) therapy. During the second course, he developed dyspnea, which gradually worsened. After admission, gastrointestinal losses of magnesium were confirmed, and intravenous magnesium was administered, which consequently improved his symptoms. Although KRd therapy was resumed, hypomagnesemia was recurring. Therefore, carfilzomib was replaced with ixazomib, which improved the patient's hypomagnesemia. The major causes of hypomagnesemia are gastrointestinal and renal losses; our case appeared to have gastrointestinal losses of magnesium and was successfully treated by discontinuing carfilzomib. Hypomagnesemia should be considered in patients receiving carfilzomib; furthermore, clinicians should consider discontinuing carfilzomib as its treatment.

Diagnostic significance of adenosine deaminase in pleural effusate for primary effusion lymphoma-like lymphoma.

Our case and review of the literature suggests the possibility that pleural effusate adenosine deaminase levels in patients with primary effusion lymphoma-like lymphoma (PEL-LL) might be much higher than those in patients with other types of lymphomas and those with tuberculous pleural effusion.