Change of hand sensation and function in patients with malignant lymphoma during early-stage vincristine chemotherapy: A single-center observational study.

This study aimed to investigate changes in hand sensation (finger tactile threshold and two-point discrimination) and function in patients with malignant lymphoma, particularly during the early stages of chemotherapy with vincristine. Eighteen patients with malignant lymphoma were enrolled in this study. Data on the Common Terminology Criteria for Adverse Events Version 4.0, the visual analog scale for hand numbness, the Semmes Weinstein monofilament test, static and moving two-point discrimination (2PD), grip strength, pinch strength, and the Purdue Pegboard test were collected at 3 time points: before the start of chemotherapy (T0), after the first cycle of chemotherapy (T1), and after the second cycle of chemotherapy (T2). No significant changes were observed in Semmes Weinstein monofilament test at T0, T1, or T2 in either hand. However, the static 2PD was significantly worse for the right ring, little, and left middle fingers, whereas the moving 2PD was significantly worse for the right ring, left index, middle, and ring fingers. Furthermore, the visual analog scale scores for hand numbness and left-hand grip strength worsened significantly. Right-hand grip strength, pinch strength of both hands, and Purdue Pegboard test showed no significant deterioration. Chemotherapy with vincristine may affect hand sensation and function in patients with malignant lymphoma by exacerbating finger 2PD and hand numbness. Additionally, during the early stages of vincristine chemotherapy, it is important to monitor for a decrease in grip strength specifically in the left hand.

An observational study of once-weekly carfilzomib in patients with multiple myeloma in Japan (Weekly-CAR study).

Background: The ARROW study demonstrated that once-weekly carfilzomib and dexamethasone (wKd) therapy significantly prolonged progression-free survival compared with twice-weekly carfilzomib and dexamethasone therapy in relapsed or refractory multiple myeloma patients. Aim: To describe the treatment patterns, effectiveness and safety of wKd therapy in real-world settings in Japan. Methods: We investigated data from the medical records of 126 Japanese patients with relapsed or refractory multiple myeloma. Results: The overall response rate was 66.3%. The median progression-free survival was 9.5 months. The incidence of treatment-emergent adverse events of any grade and grade ≥3 were 45.8 and 20.8%, respectively. Conclusion: There were no new or unexpected safety signals in this study. This study demonstrated the effectiveness and safety profiles of wKd therapy in Japan.

Carfilzomib became available for daily clinical practice as a drug for cancer of bone marrow (multiple myeloma) that comes back or does not respond to previous drug (relapsed or refractory). This drug was approved in the USA in 2012, and in Japan in 2016. In this study, we looked at how once-weekly carfilzomib works and how safe it is in real-life situations in Japan. We screened 126 patients with relapsed or refractory multiple myeloma in Japan. The median age of the patients was 70 years, with 25% being over 75 years. This study also included some patients who were not in the best overall health, had a history of many treatments or had heart complications. In 66.3% of patients, the cancer had disappeared or the extent of the cancer had reduced after treatment. Side effects and serious side effects occurred in 45.8 and 14.2% of patients, respectively. The most common side effects were low levels of blood platelets (9.2%), high blood pressure (5.8%), loose or watery stools (5.0%), fever (5.0%), and low levels of red blood cells (4.2%). Heart disorders occurred in five patients. But all patients recovered or improved with treatment such as blood pressure lowering drugs and diuretics. These results showed that once-weekly carfilzomib works well and is safe in real-world settings in Japan. This information can help us think about how to pick the right patients and handle heart disease risks when using carfilzomib treatment.

Is Phase Angle Useful in Screening for Sarcopenia in Patients with Hematologic Malignancies?

The purposes of this study were to investigate the relationship between sarcopenia and phase angle (PhA), and to examine whether PhA cutoff values can be used to identify sarcopenia in patients with hematologic malignancies. The study population comprised 108 patients with hematologic malignancies who were admitted for chemotherapy, and were undergoing rehabilitation for exercise therapy. The diagnostic criteria for sarcopenia were determined according to the Asian Working Group for Sarcopenia 2019. Muscle strength, endurance, and body composition (including PhA), were assessed. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to investigate associations between sarcopenia and PhA, and to determine cutoff values. Sarcopenia was found in 17.6% of the participants. PhA was significantly associated with sarcopenia (p < 0.01). The areas under the curve were 0.84 for the males and 0.87 for the females, and the cutoff values were 4.75° for the males (sensitivity 69%, specificity 83%) and 3.95° for the females (sensitivity 78%, specificity 85%). Our results suggest that PhA, which can be measured noninvasively, objectively, and rapidly, can be used as a screening tool for sarcopenia in patients with hematologic malignancies.

Impact of Sarcopenia on Outcome of Exercise Therapy in Older Non-Hodgkin Lymphoma Patients.

PURPOSE: The aim of this study was to investigate the effects of exercise therapy on physical function and quality of life (QOL) in older patients with non-Hodgkin lymphoma undergoing inpatient chemotherapy, including differences between patients with and without sarcopenia. METHODS: Thirty-one inpatients aged 70 years or older participated in this study. Grip and knee extensor strength, 6-minute walking test, body composition, nutritional status, fatigue and health-related QOL at admission and discharge were compared. In addition, the patients were classified into sarcopenic and non-sarcopenic groups, and a comparison between admission and discharge and 2-way ANOVA were performed. RESULTS: Overall, grip strength and skeletal muscle mass were significantly lower at discharge than at admission (P < .05); however, QOL significantly improved (P < .05). In the non-sarcopenia group, grip strength, right knee extension muscle strength, and skeletal muscle mass were all significantly lower at discharge than at admission (P < .05); however, this was not the case in the sarcopenia group. In terms of QOL, improvements were observed in different items in the non-sarcopenia and sarcopenia groups. There was a significant interaction between admission to discharge time period and sarcopenia regarding left grip strength, right knee extensor strength, and QOL. CONCLUSION: Exercise therapy is effective in improving QOL in older non-Hodgkin lymphoma patients undergoing inpatient chemotherapy. However, the effect of exercise therapy and optimal exercise load may differ between non-sarcopenia and sarcopenia patients. Therefore, it is necessary to consider exercise therapy in the future, taking into account the presence or absence of sarcopenia.

Exacerbation of autoimmune hemolytic anemia associated with pure red cell aplasia after COVID-19: A case report.

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are rare complications of coronavirus disease 2019 (COVID-19). Herein, we report the case of a 28-year-old Japanese man who showed severe AIHA exacerbation associated with PRCA after COVID-19. AIHA was diagnosed and maintained for 5 years. Approximately 4 weeks after COVID-19, the patient developed severe anemia (hemoglobin level, 3.4 g/dL). Laboratory test results confirmed hemolytic exacerbation of IgG-mediated warm-type AIHA. Despite the hemolysis phase, the bone marrow revealed extreme hypoplasia of erythroblasts with a decreased reticulocyte count, similar to that observed in patients with PRCA. During oral prednisolone treatment, the patient recovered from anemia and showed increased reticulocyte count and reduced hypoplasia of marrow erythroblasts. Exacerbation of AIHA and PRCA was triggered by COVID-19 because other causes were ruled out. Although this case report highlights that COVID-19 could lead to hematological complications such as AIHA and PRCA, the exact mechanisms remain unclear.

Outcomes of adult patients with early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) and non-ETP T-ALL.

Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) is generally considered to be a high-risk subtype. We retrospectively analyzed the clinical outcomes of adult patients diagnosed with ETP-ALL or other T-cell ALL (non-ETP T-ALL). The subjects were 82 patients (ETP-ALL: n = 18, non-ETP T-ALL: n = 64) for whom relevant immunophenotype data needed for classification were available. ETP-ALL patients were older (median age, 50.5 vs. 33.5 years, P = 0.042) and had less mediastinal involvement (27.8 vs. 73.4%, P < 0.001). The rate of complete remission (CR) with the first induction therapy was significantly lower in the ETP group (33.3 vs. 64.0%, P = 0.03), but the CR rate within 2 cycles of chemotherapy did not differ significantly (61.1 vs. 76.6%, P = 0.232). The 3-year overall survival (OS) rate was also similar in both groups (43.2 vs. 45.8%, P = 0.992). The ETP phenotype had no impact on survival in the transplant group or the non-transplant group. A multivariate analysis identified the male sex as a poor prognostic factor (HR: 4.43, P < 0.01), but not the immunophenotype of ETP. The prognosis for adult patients with ETP-ALL was comparable to that of non-ETP T-ALL patients. However, further studies aimed at improving the remission rate for ETP-ALL are needed.

Physical function, nutritional status, and quality of life before and after chemotherapy in patients with malignant lymphoma.

This study investigates the efficacy of and gender differences in exercise therapy in patients with malignant lymphoma undergoing chemotherapy. Twenty-six patients (13 men, 13 women) received physical therapy (based on the Borg Scale 13) during hospitalization. Physical function was measured using grip and knee extension strength, 6-minute walking distance, and body composition; nutritional status assessed via Mini Nutritional Assessment (MNA®); and serum albumin levels analyzed. Fatigue was evaluated using the Brief Fatigue Inventory, and health-related quality of life was assessed with the Medical Outcome Study 36-Item Short-Form Health Survey (SF-36v2). The analysis of all patients indicated that the right grip strength, skeletal muscle mass, skeletal muscle index, and leg muscle mass significantly decreased, whereas the serum albumin level, MNA® score, and scores of many items of the SF-36v2 significantly increased after chemotherapy. In a gender-specific analysis, only men showed significant declines in the skeletal muscle mass and skeletal muscle index, and improvement in the MNA® score after chemotherapy. In the SF-36v2, there were significant improvements in general health and physical component summary scores among men, and general health and mental component summary scores among women. Exercise therapy at a Borg Scale intensity of 13 may not prevent muscle mass decline in patients with malignant lymphoma, especially male patients. In addition, this study revealed that there is a gender difference in the effect of exercise therapy on quality of life. Thus, gender should be considered in exercise therapy for patients with malignant lymphoma.

Development of multiple myeloma after 15 years of treatment for polycythemia vera and successful treatment using bortezomib: A case report.

Multiple myeloma (MM) and polycythemia vera (PV) rarely coexist; the clinical manifestations and treatment of this coexistence have not been described. An 81-year-old woman developed MM 15 years after undergoing PV treatment and was successfully treated using bortezomib. Herein, we share our experience of treating MM under such unusual conditions.

Physical therapy for multiple myeloma patients with severely hindered daily living activities due to bone lesions: a report of two cases.

[Purpose] Physical therapy for patients with multiple myeloma requires appropriate exercise intensity and risk management due to osteolytic lesions. However, the optimal strategy for setting exercise intensity remains unclear. We report cases in which physical therapy was performed using the Borg scale and the Common Terminology Criteria for Adverse Events v4.0 as indicators of improvement in the performance of activities of daily living without causing adverse events. [Participants and Methods] Two patients with multiple myeloma, whose performance status was 4, underwent resistance training of the upper and lower limbs and activities of daily living practice in stages according to their functional status. Each exercise was performed for 20 to 40 minutes twice a day for 6 days a week. The exercise intensity was set to 13 on the Borg scale as a guide, and the allowable bone pain was up to Grade 1 according to Common Terminology Criteria for Adverse Events v4.0. [Results] No adverse events occurred in either patient, and the performance status improved to 1 or 2. Subsequently, autologous peripheral hematopoietic stem cell transplantation was performed. [Conclusion] Physical therapy with exercise intensity set to 13 on the Borg scale and Grade 1 per Common Terminology Criteria for Adverse Events v4.0 may safely improve the performance of activities of daily living of patients with multiple myeloma.

Weight Loss Intervention before Cord Blood Transplantation in an Obese Patient with Acute Myeloid Leukemia: A Case Study.

BACKGROUND: A severely obese woman (39.8 kg/m2) with relapsed acute myeloid leukemia was admitted to our hospital to undergo salvage chemotherapy followed by cord blood transplantation (CBT). CASE: During the salvage chemotherapy period, a 70-day weight loss program addressing diet and exercise was administered. After the 70-day intervention, the patient's body weight and body fat mass had decreased (8.6% and 15.0%, respectively) without any adverse events. The number of available cord blood units with total nucleated cells per body weight greater than 2 × 107/kg was zero at admission and two after weight loss; therefore, CBT could be performed. DISCUSSION: Considering this case, we suggest that a weight loss program combining exercise and nutrition therapy may help patients scheduled for hematopoietic stem cell transplantation by focusing on risk management.

Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with hepatitis-associated aplastic anemia.

Outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) for hepatitis-associated aplastic anemia have not been fully evaluated. In the present study, the outcomes of 37 adult patients with hepatitis-associated aplastic anemia who underwent allogeneic HSCT were retrospectively analyzed using the registry database of Japan Society for Hematopoietic Cell Transplantation. The median age of the patients was 24 years (range, 16-61). The median period between diagnosis of hepatitis-associated aplastic anemia and HSCT was 6.0 months (range, 0.5-430.8). Stem cell sources were bone marrow (N = 19) or peripheral blood stem cells (N = 5) from an HLA-identical sibling or bone marrow (N = 11) and cord blood (N = 2) from an unrelated donor. The majority of conditioning regimens were fludarabine-based or high-dose cyclophosphamide-based. In all but 2 cases of early death, neutrophil engraftment was achieved. At the time of analysis, 32 patients were alive, with a median follow-up of 54.1 months. Five-year overall and failure-free survival rates were 86.0% (95% CI, 69.4-93.9%) and 75.0% (95% CI, 57.4-86.2%), respectively. Despite the heterogeneity in transplant procedures in a small number of patients, these results suggest that allogeneic HSCT is safe for use in hepatitis-associated aplastic anemia with a low rate of transplant-related mortality.

Dysregulation of the MIRLET7/HMGA2 axis with methylation of the CDKN2A promoter in myeloproliferative neoplasms.

Overexpression of high mobility group AT-hook 2 (Hmga2), which is negatively regulated by MIRLET7 micro RNAs through 3'-untranslated region (3'UTR), causes proliferative haematopoiesis mimicking myeloproliferative neoplasms (MPNs) and contributes to progression of myelofibrosis in mice. Thus, we investigated HMGA2 mRNA expression in 66 patients with MPNs including 23 polycythaemia vera (PV), 33 essential thrombocythaemia (ET) and 10 primary myelofibrosis (PMF). HMGA2 mRNA expression, especially variant 1 with 3'UTR that contains MIRLET7-specific sites, rather than variant 2 lacking 3'UTR, is frequently deregulated due to decreased MIRLET7 expression in granulocytes from over 20% of PV and ET, and in either granulocytes or CD34(+) cells from 100% of PMF. Patients with deregulated HMGA2 mRNA expression were significantly more likely to show splenomegaly, high serum lactate dehydrogenase values, and methylation of the CDKN2A promoter compared with other patients without deregulation of HMGA2. A histone deacetylase inhibitor, panobinostat, significantly increased MIRLET7 expression and reduced variant 1 of HMGA2 mRNA expression, but not variant 2, in both U937 cells and PMF-derived CD34(+) cells. Moreover, both panobinostat and small interfering RNA of HMGA2 demethylated the CDKN2A promoter in U937 cells. In conclusion, the frequently dysregulated MIRLET7/HMGA2 axis could be a therapeutic target in MPNs.

Recurrent extramedullary relapse of acute promyelocytic leukemia after allogeneic stem cell transplantation: successful treatment by arsenic trioxide in combination with local radiotherapy.

Isolated extramedullary relapse is rare in patients with acute promyelocytic leukemia (APL) after allogeneic stem cell transplantation (SCT), and an optimal therapy for it has not been established. We describe a patient with APL who developed serially occurring extramedullary disease (EMD) after SCT. We confirmed that EMD had arisen from the recipient's APL blasts by detecting t(15;17) and PML/RARalpha from the tumor cell suspension. The patient displayed EMD 4 times at different sites. Administration of all-trans retinoic acid with local radiotherapy and with chemotherapy for the first to third EMDs resulted in regression of the tumors. However, these regimens did not prevent the subsequent occurrence of new EMD. For the fourth EMD, intravenous administration of arsenic trioxide followed by local radiotherapy resulted in the disappearance of EMD, and no further EMD has developed to date. In the present case, the bone marrow was in morphologic and molecular remission during the course of recurrent EMD. The accumulation of detailed cases is needed to elucidate the pathogenesis, predisposing factors, and optimal therapy for EMD in APL after SCT.

Philadelphia chromosome-positive acute lymphoblastic leukemia rescued with a second allogeneic stem cell transplantation from a haploidentical mother after relapse following cord blood transplantation.

A 32-year-old female patient who had Philadelphia chromosome-positive acute lymphoblastic leukemia underwent cord blood transplantation while in her second remission. However, she had a hematological and central nervous system relapse 3 months later. After reinduction with imatinib mesylate, unmanipulated peripheral blood stem cell transplantation was performed from the patient's haploidentical mother with a reduced-intensity conditioning regimen. Rabbit antithymocyte globulin, tacrolimus, and methylprednisolone were used for prophylaxis of graft-versus-host disease. Engraftment of neutrophils was observed on day 12, and complete donor chimerism was obtained by day 24. The posttransplantation course was uneventful. Although the patient had a relapse 10 months later, this case demonstrated that transplantation from a haploidentical donor is clearly a feasible alternative for patients who desperately need rescue transplantation.

Phenotypes and phosphatidylinositol glycan-class A gene abnormalities during cell differentiation and maturation from precursor cells to mature granulocytes in patients with paroxysmal nocturnal hemoglobinuria.

To define the phosphatidylinositol glycan-class A (PIG-A) gene abnormality in precursor cells and the changes of expression of glycosylphosphatidylinositol-anchored protein and contribution of paroxysmal nocturnal hemoglobinuria (PNH) clones with PIG-A gene abnormalities among various cell lineages during differentiation and maturation, we investigated CD59 expression on bone marrow CD34(+) cells and peripheral granulocytes from 3 patients with PNH and the PIG-A gene abnormalities in the CD59(-), CD59(+/-), and CD59(+) populations by nucleotide sequence analyses. We also performed clonogeneic assays of CD34(+)CD59(+) and CD34(+)CD59(-) cells from 2 of the patients and examined the PIG-A gene abnormalities in the cultured cells. In case 1, the CD34(+) cells and granulocytes consisted of CD59(-) and CD59(+) populations and CD59(-), CD59(+/-), and CD59(+) populations, respectively. Sequence analyses indicated that mutation 1-2 was in the CD59(+/-) granulocyte population (20 of 20) and the CD34(+)CD59(-) population (2 of 38). In cases 2 and 3, the CD34(+) cells and granulocytes consisted of CD59(+) and CD59(-) cells. Sequence analyses in case 3 showed that mutation 3-2 was not in CD34(+)CD59(-) cells and was present in the CD59(-) granulocyte population. However, PIG-A gene analysis of cultured CD34(+)CD59(-) cells showed that they had the mutation. This analysis also revealed that there were some other mutations, which were not found in CD34(+)CD59(-) cells and CD59(-) or CD59(+/-) granulocytes in vivo, and that sometimes they were distributed specifically among different cell lineages. In conclusion, our findings suggest that PNH clones might contribute qualitatively and quantitatively differentially to specific blood cell lineages during differentiation and maturation of hematopoietic stem cells.