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Background: Some chemotherapeutic agents cause carnitine deficiency, which causes general fatigue. However, there is no study on carnitine deficiency in patients with chronic myeloid leukemia (CML) during tyrosine kinase inhibitor (TKI) therapy. Objective: In this study, we investigated carnitine concentrations in patients with CML receiving TKI therapy. Method: This study included patients with well-controlled CML. Total carnitine and free carnitine concentrations were evaluated using the enzyme cycling method. The brief fatigue inventory (BFI) and cancer fatigue scale (CFS) were used to assess general fatigue developed during TKI therapy. Results: Fifty-five patients on TKI therapy were included. Of these, 12 (21.8%) patients had low free carnitine concentrations. Free carnitine concentrations were higher in men than in women. Younger age was closely associated with lower free carnitine concentrations. TKI type, TKI dose, treatment response, or therapy duration were not associated with free carnitine concentrations. None of the scores (the global fatigue score with the BFI and CFS score) correlated with carnitine concentrations. Concentrations of free carnitine in patients in the treatment-free remission group were slightly higher than those in the TKI group, with only 9.1% having a low concentration of free carnitine. Conclusion: Carnitine deficiency is probably not a major cause of general fatigue but may occur in patients with CML receiving TKI therapy.

Background/Aim: We assessed the prognosis of patients with refractory or relapsed multiple myeloma (RRMM) by focusing on the change in absolute lymphocyte counts (ALCs) after lenalidomide and dexamethasone (Ld) initiation. Patients and Methods: In total, 72 patients with RRMM were treated with Ld. ALCs were evaluated before treatment and at 1, 2, and 3 months after Ld initiation. The median ALCs in the entire cohort before and at 1, 2, 3 months after Ld initiation were 1,131, 1,059, 1,222, and 1,162/μl, respectively. Results: ALCs before Ld initiation did not affect time to next treatment (TNT) or overall survival (OS). However, the patients with ALCs equal to or greater than the median at 3 months showed relatively better TNT than those with lower lymphocyte counts, with a significant difference. OS was also significantly longer in patients with higher ALCs. Conclusion: Immunomodulation by lenalidomide may improve prognosis in patients with RRMM.

Background/Aim: Here, we investigated whether bortezomib as a maintenance therapy affected outcomes in transplant-ineligible patients with multiple myeloma (MM). Patients and Methods: Following induction therapy with bortezomib, maintenance therapy with bortezomib (1.3 mg/m2) and dexamethasone (20 mg) was administered once or twice every 4 weeks until disease progression. The endpoints of this study were time to next treatment and overall survival. Results: Seventy-six newly diagnosed, transplant-ineligible patients were treated with a bortezomib-based regimen; 28 discontinued induction therapy, 27 did not receive maintenance therapy after induction therapy (the non-maintenance group), and 21 did (the maintenance group). In the three groups, the median times to the next required treatment were 3, 14, and 37 months, respectively. The 3-year overall survival rates were 55%, 69%, and 85%, respectively. There were no significant differences in patient characteristics between the non-maintenance and maintenance groups, except for poorer estimated glomerular filtration rates in the maintenance group. Conclusion: Bortezomib maintenance therapy may be a useful option for transplant-ineligible patients with MM.

The use of bortezomib in the clinic has significantly improved outcomes for patients with multiple myeloma (MM), even those harboring high-risk cytogenetic abnormalities or those classified in the high-risk category according to the International Staging System (ISS). In this study, we analyzed the association between immunophenotyping on myeloma cells and the clinical outcomes of patients who received bortezomib-based regimens as first-line therapy. Immunophenotypic analysis before bortezomib therapy was performed by flow cytometry, and whether the immunophenotyping results influenced the clinical outcomes of the patients was investigated. Seventy-four newly diagnosed patients with MM were included in this study. We found that the expression of MPC-1 significantly predicted the time to next therapy (TNT), with a longer TNT in the MPC-1 positive group (p = 0.005), whereas it did not affect overall survival (OS; p = 0.773). In addition, we found that CD45-positivity was associated with shorter TNT (p = 0.0432). Following ISS assessment at treatment initiation, patients who were classified as stage I showed a slightly longer OS compared to those at stage II or III; however, these results were not significant (p = 0.0987). Furthermore, multivariate analysis revealed the prognostic significance of MPC-1 expression, as MPC-1-negativity was associated with a worse TNT. The combination of MPC-1 and CD45 status more sensibly predicted the TNT for bortezomib therapy. Our results demonstrate the clinical importance of immunophenotyping on myeloma cells to determine patient prognoses in this era of novel therapeutic agents.

During mouse ontogeny, hematopoietic cells arise from specialized endothelial cells, i.e., the hemogenic endothelium, and form clusters in the lumen of arterial vessels. Hemogenic endothelial cells have been observed in several embryonic tissues, such as the dorsal aorta, the placenta and the yolk sac. Recent work suggests that the mouse embryonic head also produces hematopoietic stem cells (HSCs)/progenitors. However, a histological basis for HSC generation in the head has not yet been determined because the hematopoietic clusters and hemogenic endothelium in the head region have not been well characterized. In this study, we used whole-mount immunostaining and 3D confocal reconstruction techniques to analyze both c-Kit+ hematopoietic clusters and Runx1+ hemogenic endothelium in the whole-head vasculature. The number of c-Kit+ hematopoietic cells was 20-fold less in the head arteries than in the dorsal aorta. In addition, apparent nascent hematopoietic cells, which are characterized by a "budding" structure and a Runx1+ hemogenic endothelium, were not observed in the head. These results suggest that head HSCs may not be or are rarely generated from the endothelium in the same manner as aortic HSCs.

Background : In myeloproliferative neoplasms, especially essential thrombocythemia (ET), platelet (Plt) counts and von Willebrand factor (vWF):Ristocetin cofactor (RCo) levels have been reported to be inversely correlated. However, there have been no reports of the comparison of high vs. low values of JAK2 allele burden and necessary of Plt counts reduction to achieve vWF:RCo levels ≥50%, which is required for major surgery. We investigated the correlation between vWF level and Plt counts for JAK2V617F mutation positive (JAK2V617F+) polycythemia vera (PV) and ET (allele burdens ≥50% and Method: We recruited patients with PV and ET who were diagnosed per the 2008 World Health Organization criteria at 3 hospitals since 2011 to 2018. All patients were analyzed at Juntendo University for JAK2 (V617F, exson12), CALR, and MPL mutations. We collected data of JAK2V617F+ or CALR+ patients. Triple-negative mutations of ET were excluded in this study because it is difficult to differentiate between ET and secondary thrombocytosis. We analyzed the correlation between Plt counts and vWF:RCo levels for three mutation groups mutations (JAK2V617F allele burden ≥50%, Results: We collected 146 PV and ET patients. Among 54 PV patients, 50 had JAK2V617F+, 3 had JAK2 exon 12, and 1 had a triple-negative mutation(s) in PV patients. Among 92 ET patients, 53 had JAK2V617F+, 35 had CALR+ (22 del52, 12 ins5 and 1 del34), and 4 had MPL mutations in ET patients. vWF:RCo levels were weakly inversely correlated with Plt counts in patients with JAK2V617F+ PV and ET from whom blood samples were obtained for the first time after enrolling in this study (Ps=-0.531 and Ps=-0.439, respectively). In contrast, vWF:RCo levels and Plt counts in patients with CALR+ ET showed a strong inverse correlation (Ps=-0.762). Interestingly, 3/50 PV and 4/53 ET patients with JAK2V617F mutations showed vWF:RCo levels >150% (normal vWF:RCo levels range: 50-150%). Furthermore, 3/50 PV and 1/53 ET patients with Plt counts 150% or During the entire observation period, 8/50 and 7/53 patients with JAK2V617F+ PV and ET, respectively, and 1/35 patients with CALR+ ET had vWF:RCo levels >150%. One case of JAK2V617F+ ET (allele burden When Plt counts were controlled to 30%. However, 13/86 patients did not achieve 50%, which is the standard for safely performing the major surgical procedures prescribed in most guidelines. In patients whose Plt counts controlled to Conclusion: For patients with CALR+ ET, we propose that vWF:RCo levels can be predicted based on Plt counts; however, it is difficult to predict vWF:RCo levels by Plt counts in JAK2V617F+ PV and ET patients because the inverse correlation between vWF:RCo levels and Plt counts was weak. Overactivation of vWF:RCo levels was often observed in JAK2+ PV and ET. Moreover, in 1 case, the patient exhibited only age as the risk factor for the complication of thrombosis. Because of these findings, overactivation of vWF:RCo levels may be one of the reasons for thrombotic events in JAK2V617F+ PV and ET. In addition, it was also found that cases of JAK2V617F+ allele burden ≥50% in PV and ET should be careful for hemorrhage in major surgery, even if Plt counts were controlled Disclosures No relevant conflicts of interest to declare.