Oncofertility is the medical field that bridges oncology and reproduction that seeks to give healthcare providers and patients the opportunity to optimize residual fertility. The treatment for ...hematological malignancies carries gonadal toxicity, so that the preservation of fertility should be considered in all patients in childhood, adolescence and young adulthood. Most patients who receive only chemotherapy remain fertile, whereas those who receive regimens consisting of high-dose alkylating agents or total body irradiation can develop permanent infertility. In postpubertal patients, there are established methods for preserving fertility, such as the cryopreservation of sperm, oocytes and embryos. Although ideally performed before the initiation of gonadotoxic treatment, these procedures for fertility preservation can be performed any time prior to the loss of gonadal function. In contrast, a standard option is not available in prepubertal patients, and the preservation of fertility must be sought through experimental methods. Future advances in reproductive medicine may overcome this limitation. Gonadal tissue cryopreservation might be performed in the hope that sperm or mature oocytes could later be extracted from cryopreserved tissue. Healthcare providers, including hematologists, reproductive endocrinologists, nurses, clinical psychotherapists and embryologists, need to optimize the patient's fertility through shared decision-making while always remaining aware of the rapidly progressing developments in reproductive medicine.
Eighty Japanese children, aged 8-12 years, with a spherical equivalent refraction (SER) of - 1.00 to - 6.00 dioptres (D) were randomly allocated into two groups to receive either a combination of ...orthokeratology (OK) and 0.01% atropine solution (combination group) or monotherapy with OK (monotherapy group). Seventy-three subjects completed the 2-year study. Over the 2 years, axial length increased by 0.29 ± 0.20 mm (n = 38) and 0.40 ± 0.23 mm (n = 35) in the combination and monotherapy groups, respectively (P = 0.03). Interactions between combination treatment and age or SER did not reach significance level (age, P = 0.18; SER, P = 0.06). In the subgroup of subjects with an initial SER of - 1.00 to - 3.00 D, axial length increased by 0.30 ± 0.22 mm (n = 27) and 0.48 ± 0.22 mm (n = 23) in the combination and monotherapy groups, respectively (P = 0.005). In the - 3.01 to - 6.00 D subgroup, axial length increased by 0.27 ± 0.15 mm (n = 11) and 0.25 ± 0.17 mm (n = 12) in the combination and monotherapy groups, respectively (P = 0.74). The combination therapy may be effective for slowing axial elongation, especially in children with low initial myopia.
Relapsed acute leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with poor prognosis. In a subset of patients, durable remissions can be achieved with a ...second allo-HSCT (allo-HSCT2). However, many patients experience relapse after allo-HSCT2 and they may be considered for a third allo-HSCT (allo-HSCT3). Nevertheless, the benefit of allo-HSCT3 remains unconfirmed. Thus, herein a retrospective analysis of 253 allo-HSCT3s in patients with relapsed/refractory acute leukemia was carried out. In total, 29 (11.5%) survived at a median follow-up of 794 days (range: 87-4 619). The 3-year leukemia-free survival and overall survival (OS) rates were 9.7% and 10.9%, respectively. Patients who maintained remission for ≥2 years after allo-HSCT2 had a significantly better 3-year OS (35.8%) than those who experienced early relapse (<1 year, 7.8%; 1-2 years, 14.0%; P = 0.004). Complete remission at allo-HSCT3, performance status score of 0-1 at allo-HSCT3, grade I acute graft-versus-host disease after allo-HSCT2, and relapse ≥2 years after allo-HSCT2 were associated with better survival in patients who received allo-HSCT3. The prognosis after allo-HSCT3 in patients with relapsed/refractory acute leukemia is generally unfavorable. However, given the lack of alternative treatment options, allo-HSCT3 may be considered in a group of patients.
Objective Dasatinib, a second-generation tyrosine kinase inhibitor, is used for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It ...reportedly causes pulmonary arterial hypertension (PAH) and the dose-dependent induction of apoptosis in pulmonary endothelial cells. However, no report has yet discussed the relationship between dasatinib-induced PAH and drug dose. We therefore investigated the incidence of dasatinib-induced PAH and the relationship between dasatinib-PAH and drug dose in consecutive patients with CML and Ph+ ALL who took dasatinib. Methods The clinical data of 128 patients with CML (94 patients) and Ph+ ALL (34 patients) were retrospectively analyzed. Patients All patients (>17 years old) who received dasatinib from January 2009 to March 2020 at Jichi Medical University (Tochigi, Japan) were included. Patients who transferred within one month of starting dasatinib administration were excluded. Results Four (4.3%) and three (8.8%) patients developed pulmonary hypertension (PH), which was considered present when the transtricuspid pressure gradient was ≥40 mmHg, in the CML and ALL groups, respectively. No significant difference was observed between the PH onset and the administration period, cumulative dose, or daily dose of dasatinib. PH occurred in seven patients (5.5%), and the period from the start of dasatinib administration to the PH onset ranged from 7 to 39 (median: 28) months. No patients died from PH in either group. Conclusion Dasatinib-induced PAH does not occur time- or dose-dependently. When administering dasatinib, cardiovascular diagnostic modalities should be routinely checked, and PAH occurrence should be promptly detected.
Purpose
To investigate the additive effects of orthokeratology (OK) and atropine 0.01% ophthalmic solution, both of which are effective procedures to slow axial elongation in children with myopia.
...Study design
Prospective randomized clinical trial.
Methods
Japanese children aged 8–12 years with a spherical equivalent refractive error of − 1.00 to − 6.00 diopters were included. A total of 41 participants who had been wearing the OK lenses successfully for 3 months were randomly allocated into two groups to receive either the combination of OK and atropine 0.01% ophthalmic solution (combination group) or monotherapy with OK (monotherapy group). Subjects in the combination group started to use atropine 0.01% ophthalmic solution once nightly from 3 months after the start of OK. Axial length was measured every 3 months using non-contact laser interferometry (IOLMaster), and the axial length measurement at month 3 of OK therapy was used as the baseline value in both groups. The increase in axial length over 1 year was compared between the two groups.
Results
A total of 40 consecutive subjects (20 subjects in the combination group and 20 in the monotherapy group) were followed for 1 year. The increase in axial length over 1 year was 0.09 ± 0.12 mm in the combination group and 0.19 ± 0.15 mm in the monotherapy group (
P
= 0.0356, unpaired
t
test).
Conclusion
During the 1-year follow-up, the combination of OK and atropine 0.01% ophthalmic solution was more effective in slowing axial elongation than OK monotherapy in children with myopia.
Graft failure (GF) is a life-threatening complication after allogeneic stem cell transplantation (SCT). Although salvage SCTs can be performed with haploidentical donor (HID) or cord blood (CB), no ...study has compared the performances of these two sources. Using nationwide registration data, we compared the transplant outcomes of patients who developed GF and underwent salvage transplantation from HID (n = 129) and CB (n = 570) from 2007 to 2016. The HID group demonstrated better neutrophil recovery (79.7 vs. 52.5% at 30 days, P < 0.001). With a median follow-up of 3 years, both groups demonstrated similar overall survival (OS) and nonrelapse mortality (NRM; 1-year OS, 33.1 vs. 34.6% and 1-year NRM, 45.1 vs. 49.8% for the HID and CB groups). After adjustments for other covariates, OS did not differ in both groups. However, HID was associated with a lower NRM (hazard ratio, 0.71; P = 0.038) than CB. The incidence of acute graft-versus-host disease (GVHD)-related deaths was significantly higher in the HID group, although infection-related deaths were observed more frequently in the CB group. HID may be a promising salvage SCT option after GF due to its faster engraftment and low NRM.
Cytomegalovirus (CMV) reactivation in cord blood transplantation (CBT) may result in the proliferation and maturation of natural killer (NK) cells. Similarly, a mismatch of the killer cell ...immunoglobulin-like receptor (KIR)-ligand induces NK cell activation. Therefore, if CMV reactivation occurs in the presence of KIR-ligand mismatch, it might improve CBT outcomes. We assessed the difference in the effect of CMV reactivation in the presence of KIR-ligand mismatch on disease relapse in the graft-versus-host direction. A total of 2840 patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, and chronic myeloid leukemia were analyzed. Among those with a HLA-Bw4/A3/A11 (KIR3DL-ligand) mismatch, CMV reactivation up to 100 days following CBT had a favorable impact on relapse (18.9% vs. 32.9%, P = 0.0149). However, this effect was not observed in cases without the KIR3DL-ligand mismatch or in those with or without a HLA-C1/C2 (KIR2DL-ligand) mismatch. The multivariate analysis suggested that CMV reactivation had a favorable effect on relapse only in cases with a KIR3DL-ligand mismatch (hazard ratio 0.54, P = 0.032). Moreover, the interaction effect between CMV reactivation and KIR3DL-ligand mismatch on relapse was significant (P = 0.039). Thus, our study reveals the association between KIR-ligand mismatches and CMV reactivation, which will enhance CBT outcomes.
Myeloablative conditioning with fludarabine/busulfan (Flu/Bu4) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) is effective for acute myeloid leukemia. However, the ...effectiveness of Flu/Bu4 for myelodysplastic syndrome (MDS) remains poorly understood. Therefore, we retrospectively analyzed nationwide registry data in Japan from 2006 to 2018 and compared transplant outcomes of adult MDS patients receiving Flu/Bu4 and busulfan/cyclophosphamide (Bu4/Cy) using propensity score (PS) matching. The primary endpoint was overall survival (OS). Among 2,482 MDS patients, 153 patients were assigned each to the Flu/Bu4 and Bu4/Cy groups. The 3-year OS rates were 52.7% (95% confidence interval CI, 43.8-60.8%) and 49.5% (95% CI, 40.8-57.6%) in the Flu/Bu4 and Bu4/Cy group, respectively (P = 0.548). The 3-year progression-free survival (P = 0.858), the cumulative incidence of relapse (P = 0.536), and cumulative incidence of non-relapse mortality (P = 0.684) were not significantly different between the two groups. According to the findings of subgroup analyses, no patient had a favorable OS when using either of the two regimens. In conclusion, although our PS-matched cohort mainly comprised older patients who had a low hematopoietic cell transplantation-comorbidity index and low-risk disease status, Flu/Bu4 could be an alternative to Bu4/Cy for MDS patients prior to allo-HSCT.
Objectives
Bloodstream infection (BSI) is a frequent complication observed in patients with febrile neutropenia (FN). BSI risk factors and incidence vary depending on chemotherapy types and ...prophylactic antimicrobial agents. We clarified these issues by post-hoc analysis of a prospective clinical trial cohort for severe FN in hematological malignancy.
Methods
We performed an intention-to-treat analysis of 413 high-risk patients and 1272 blood culture sets.
Results
Overall, 356 patients (86.2%) developed FN, and 20.8% had BSI complications. Prophylactic antimicrobials did not prevent complications of FN and BSI, but the incidence of BSIs of Gram-negative (GN) bacteria was lower than in the non-prophylaxis group (23.8% vs. 56.7%). Multinational Association of Supportive Care in Cancer (MASCC) scores < 20 were significantly correlated with the incidence of BSI, whereas MASCC scores > 21 were not (41.7% vs. 17.2%). The only significant risk factors were hypotension and dehydration. axillary temperatures were higher in GN-caused BSIs than in Gram-positive-caused BSIs and in patients with negative blood culture results (38.7 °C vs. 38.2 °C vs. 38.0 °C). The higher the fever, the higher the incidence of BSI and GN bacteremia.
Conclusions
MASCC score and axillary temperature are strong predictors of BSI. Non-administration of prophylactic antimicrobials and GN-caused BSI are correlated.
The clinical trial registration number
UMIN00010411.
Tyrosine kinase inhibitor (TKI) administration after allogeneic hematopoietic stem cell transplantation (HSCT) may carry a survival benefit in Philadelphia chromosome‐positive acute lymphoblastic ...leukemia (Ph+ ALL). Therefore, we investigated whether TKI prophylaxis for negative‐minimal residual disease (MRD) after HSCT would improve patient outcomes in this nationwide retrospective cohort study. We included patients with Ph+ ALL who underwent their first allogeneic HSCT between 2001 and 2016, received TKI before HSCT, and achieved negative‐MRD status within 180 days after HSCT. Of 850 patients for inclusion, 50 patients received TKI prophylaxis, mostly imatinib or dasatinib (median dose: 400 mg with imatinib and 40 mg with dasatinib). In a multivariate analysis, disease status at HSCT was the sole risk factor for relapse (hazard ratio, 3.58; P < .001 for positive‐MRD with complete remission CR and hazard ratio, 6.13; P < .001 for active disease). TKI prophylaxis was not associated with a decreased risk of relapse or superior overall survival in either the whole cohort or in the analysis limited to negative‐MRD or positive‐MRD with CR1 at HSCT. Meanwhile, TKI prophylaxis limited to dasatinib might be associated with a decreased risk of relapse (hazard ratio, 0.34; P = .140), unlike imatinib. Alternative strategies using new‐generation TKI for high‐risk patients are warranted to improve the outcomes after allogeneic HSCT.
Tyrosine kinase inhibitor prophylaxis was not associated with a decreased risk of relapse or superior overall survival despite MRD positivity at HSCT. Disease status at HSCT was a significant risk factor for relapse even in patients who achieved negative‐MRD early after HSCT.
PDF
