Hematology/ Oncology and Stem Cell Therapy最新文献

Background: Therapy-related acute myeloid leukemia (tAML) is a serious complication in patients with Non-Hodgkin lymphoma (NHL) exposed to chemotherapy or radiation. This extensive database study aims to quantify the risk of tAML in NHL and determine the impact of tAML on the overall survival (OS) of patients with NHL.

Materials and methods: Patients diagnosed with NHL and de novo AML from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results database. Multiple primary standardized incidence ratio (SIR) sessions of the SEER*Stat software were used to calculate SIR and the absolute excess risk of tAML. Overall survival (OS) was evaluated using Kaplan-Meier curves and compared using log-rank tests. Multivariate analysis was used to study the role of each covariate on OS in patients with tAML.

Results: The SIR of tAML was 4.89 (95% CI 4.41-5.41), with a higher incidence of tAML observed for age <60 years, NHL prior to 2013 and within 5 years of diagnosis, and those who received chemotherapy. NHL patients with tAML had lower OS than those without tAML (5-year OS 59% vs. 13%, p < 0.001). Patients with tAML showed worse OS than de novo AML in univariate analysis (5-year OS 13% vs. 25%, p = 0.001) but not in multivariate analysis (HR 0.93, 95% CI 0.82-1.04, p = 0.21). Age ≥60 years and lack of chemotherapy were associated with poor OS in tAML subcategory.

Conclusion: Age, time since NHL diagnosis, and receipt of chemotherapy directly influence the risk of development of tAML in NHL survivors.

Background and objectives: Intraluminal therapies, including brachytherapy, can locally destroy obstructing tumors and increase the duration of catheter/stent patency in patients with unresectable malignant biliary obstruction (MBO). In this prospective observational study, the safety and efficacy of percutaneous transhepatic biliary drainage (PTBD) followed by HDR intraluminal brachytherapy (ILBT) in the palliative treatment of malignant biliary obstruction was evaluated.

Patients and methods: In total, 66 MBO patients (January 2021 to March 2022) who were unfit for alternate treatment modalities were enrolled in our study and underwent percutaneous transhepatic biliary drainage (PTBD) with internalization. Additionally, 11 patients underwent subsequent ILBT, which was administered over two sessions (800 cGy each session, one week apart) with iridium-192 prescribed at 1.5 cmfrom the central axis of the catheter via a percutaneous biliary catheter. The second session was followed up by endoluminal stenting in the same sitting. Patients with an Eastern Cooperative Oncology Group (ECOG) status <4 and a 50% decline in bilirubin/<5 mg/dL on day 10 after PTBD were selected for ILBT. The biliary stent/catheter patency period, survival duration, mean bilirubin level (mg/dL) decline, and incidence of complications were evaluated.

Results: Among the sixty-six patients included and classified into ILBT or PTBD-only groups, the median survival period for the ILBT group vs PTBD group was 172 (84.5-273.5) days vs 45 (30.75-83) days (p ≤ 0.0001) with an overall survival (OS) at 6 months of 62.34% vs 3.64% (p ≤ 0.0001). The stent/catheter patency period of the ILBT group in comparison to the PTBD group was 172 (83-273.5) days vs 30 (20-42.5) days (p ≤ 0.0001). No major treatment-related complications were observed in any of the patients.

Conclusions: ILBT with stenting is a safe option for improving stent patency and survival duration with minimal complications with the condition that patients are carefully selected.

Background and objectives: A hematopoietic stem cell transplant (HSCT) includes a conditioning regimen which may cause unwanted metabolic changes. We analyzed the changes in electrolytes, glucose, urea, and glomerular filtration rate in patients with multiple sclerosis (MS) who underwent an autologous HSCT employing the "Mexican method."

Patients and methods: Serum and urinary electrolytes, blood glucose, creatinine, uric acid, and estimated glomerular filtration rate (eGFR) were prospectively assessed on days -11, -9, and 0 in a group of 75 patients with MS receiving an autologous HSCT employing the "Mexican method," which includes high doses of both cyclophosphamide (Cy, 200 mg/kg) and rituximab (1000 mg).

Results: The median age of the patients was 46 years, with a range of 20-65. Baseline data were defined at day -11 of the HSCT. There were significant changes in serum and urinary electrolytes, which diminished substantially after the delivery of high-dose Cy; 12 patients (16%) developed hyponatremia and 2 had hyponatremia-induced seizures, which resulted in hospital admissions. A comparison of baseline blood metabolites with those obtained after the full Cy dosage (day 0) revealed a significant increase in blood glucose and uric acid levels with an associated decrease in serum calcium, sodium, and potassium levels. The salient findings were drug-induced hyponatremia and hyperglycemia.

Conclusion: Significant changes in serum electrolytes, blood glucose, creatinine, uric acid, and estimated glomerular filtration rate (eGFR) were observed in patients given autologous HSCT for MS employing high-dose Cy. Some of these changes may have clinical consequences, mainly those derived from iatrogenic hyponatremia. No evidence of damage to renal function was observed at day 0.

Hematopoietic stem cell transplantation (HSCT) has been considered curative for children with high-risk acute leukemia (ALL), offering better survival. Short tandem repeat has been used as a marker of chimerism status after HSCT. The appearance of recipient cells >1% post-allogeneic stem cell transplant is defined as mixed chimerism (MC). Chimeric studies post-HSCT are dynamic. This study aimed to investigate the significance of recipient cells in post-HSCT pediatric ALL patients as a predictor of relapse of their primary disease. The rate of MC was 51.4% (19 out of 37 recipients). It was 48.6% (n = 18) during Day+100 and 12.9% (4 out of 31 recipients) during post-Day+100 follow-up until two years. No significant association was noted between MC and all grade overall acute graft-versus-host disease. A mortality rate of 35.1% (n = 13) and a median follow-up of 56.9 months (95% CI: 39.7-74.2) were observed for all but four (16.7%) of the survivors in remission. Regarding causes of death, transplant-related mortality was recorded in only 2 of 13 expired patients (15.4%); both succumbed to sepsis. No significant association was found between MC and primary causes of death. The cumulative probability of five-year overall survival and event-free survival was not found to be statistically significantly different for MC (≤1.0% vs. > 1.0%). In conclusion, our data did not show MC testing alone as an effective prognostic marker for detecting relapse; molecular and flow cytometric analyses should be considered in children with ALL post-HSCT for monitoring relapse.

Background and objective: Hematopoietic stem cell transplant (HSCT) is a well-established treatment for hematologic malignancies and certain autoimmune and congenital conditions. HSCT is associated with immunocompromise and increased risk of infections. This study assessed whether invasive pulmonary aspergillosis (IPA) affects in-hospital mortality and 30-day readmission among HSCT patients. A secondary objective was to examine potential differences in complications between HSCT with and without IPA.

Materials and methods: A retrospective study of a nationally representative cohort of hospital admissions was conducted, with data collected from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmissions Database between 2013 and 2019. The International Classification of Diseases, 10th revision (ICD-10), and 9th revision (ICD-9) diagnostic codes were used to identify patients with IPA and HSCT. All adult patients ≥18 years were included in the study.

Results: There were 90,451 hospitalizations for HSCT from 2013 to 2019; 89,331 (98.8%) had HSCT without IPA, while 1092 (1.2%) hospitalizations had HSCT with IPA. The in-hospital mortality for HSCT-IPA was higher compared to HSCT without IPA (18.3% vs. 4.2%; p < 0.001). HSCT-IPA had a significantly higher 30-day readmission rate (36.2%) than that of HSCT without IPA (24.0%). HSCT-IPA also had a higher mean cost of admission ($303,437) than that of HSCT without IPA ($57,587).The HSCT-IPA group had higher multi-organ complications, including respiratory failure (51.3% vs. 13.5%, p < 0.001), sepsis (38.2% vs. 18.5%, p < 0.001), septic shock (16.1% vs. 5.1%, p < 0.001), need for mechanical ventilation (21.1% vs. 5.1% p < 0.001), non-invasive positive pressure ventilation (4.9% vs. 2.5%, p < 0.001), and intensive-care unit admission (21.8% vs. 6.1% p < 0.001).

Conclusion: IPA is a rare but severe complication associated with HSCT, with higher in-hospital mortality, complications due to multi-organ failure, readmission rates, and cost of hospitalization when compared to HSCT without IPA.

Background: Chronic graft-versus-host disease (cGVHD) is a common cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Tyrosine kinase inhibitors (TKIs), including ruxolitinib, imatinib, and ibrutinib, have shown promising efficacy in cGVHD treatment.

Method: A total of 43 patients who developed cGVHD and received at least one line of TKI therapy for cGVHD treatment were evaluated retrospectively. The overall response, clinical benefit (CB), corticosteroid dose reduction, failure-free survival (FFS), and overall survival (OS) were assessed.

Result: A total of 62 lines of TKI therapy were evaluated, including ruxolitinib (n = 18), ibrutinib (n = 13), and imatinib (n = 31). With a 12-month median follow-up duration, 19/58 (32.8%), 20/41 (48.7%), and 17/29 (58.6%) responded to TKI therapy at 3, 6, and 12 months, respectively. The CB was observed in 80% of patients over time, allowing prednisone dose reduction in all 3 TKIs. The FFS rate at 12 months was higher in the imatinib (71%) and ruxolitinib groups (67%) than in the ibrutinib group (46%), while the OS rate at 12 months was similar among the three groups at 96%-100% in patients. In the sclerotic GVHD patient subgroup (n = 39), the overall response rate gradually increased over time. Ruxolitinib appeared to be as effective as imatinib and gradually improved the photographic range of motion score in sclerotic GVHD patients.

Conclusion: TKI drugs ruxolitinib, imatinib, and Ibrutinib are effective and feasible for cGVHD treatment. Ruxolitinib is as effective as imatinib for sclerotic GVHD.

Background: Sickle cell disease (SCD) is frequently inherited worldwide. The severity of SCD ranges from mild to severe, and the disease involves multiple complications, including pulmonary hypertension, stroke, recurrent vaso-occlusive crises, end-organ damage, and an increased mortality risk. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option for patients with SCD.

Objectives of the study: The objective was to assess the quality of life of adolescent and adult patients with SCD receiving HCT pre-and post-transplant.

Methods: An analytical cross-sectional study was conducted. Patients with SCD with at least one year of follow-up after HCT were interviewed to assess their quality of life pre-and post-transplant. This study was conducted at the Transplant Center of King Abdulaziz Medical City, Riyadh. The participants were identified through non-probability consecutive sampling. The FACT-G questionnaire was used to assess the quality of life domains.

Results: Thirty-one patients were included. The median age of the respondents was 32 ± 6.3 years, and 16 were male (51.6%). The most frequent indication for stem cell transplantation (58%) was a vaso-occlusive crisis. The mean FACT-G scores pre- and post-transplantation were 55.2 ± 18.17 and 91 ± 14.58, respectively. The mean number of annual ER visits was significantly reduced from 27.3 pre-transplant to 6.6 post-transplant (P-value = 0.006). Of the respondents, 51.6% experienced no severe complications post-transplantation, and most (93.5%) reported improved quality of life.

Conclusion: HCT significantly improved the quality of life of adult patients with SCD, with improvements in most FACT-G score domains. Although it was not measured by the FACT-G, the frequency of ER visits and hospital admissions were reduced significantly post-transplant, reflecting an improvement in the quality of life and a reduction in the cost of therapy for patients with SCD.

Background and objectives: Several strategies and procedures have been described for thawing umbilical cord blood (UCB) products. The ideal method for each center depends on the resources, staff training, and access to each of these. We retrospectively evaluated the incidence of side effects using the bedside thaw method after unrelated UCB transplantation.

Patients and methods: For 34 children, patient, donor, graft characteristics, and side effects were identified. In addition, we attempted to identify the risk factors that could be associated with side effects.

Results: 68% of patients experienced any adverse reaction. All the reactions were mild and transient events. The most frequent side effects were vomiting, hypertension, hemolytic reactions, and fever. There were more gastrointestinal events with a faster infusion rate.

Conclusion: The thawed at the bedside method is a practical, easy, and safe technique for cord blood transplantation in pediatric-patient settings.

Background: Therapeutic advances in acute promyelocytic leukemia (APL) have transformed it into today's most curable form of leukemia. However, recommended agents, including arsenic trioxide, idarubicin, or daunorubicin, are not easily available in low-middle-income countries, where outcomes remain suboptimal. We aimed to assess the efficacy and safety of more accessible anthracyclines.

Methods: We conducted a retrospective cohort study including sixty-one patients diagnosed with APL over a 15-year period. Patients received low-dose all-trans retinoic acid (ATRA, 25 mg/m²) with mitoxantrone or doxorubicin as an induction to remission therapy. Groups were compared using the χ² and Student's t-tests. Kaplan-Meier analysis was used for survival analyses.

Results: Thirty (49.18%) patients received mitoxantrone, and 31 (50.82%) received doxorubicin. The median follow-up was 24.6 months (1-146). Twenty-eight (93.3%) patients achieved complete remission (CR) in the mitoxantrone group and 28 (87.1%) in the doxorubicin group (p=0.103), and the median time to CR was 40 and 31 days, respectively. Mitoxantrone had a 6.7% early mortality rate and a 16.7% relapse rate compared with doxorubicin (3.2% and 32.3%, respectively). No differences were found in survival (p = 0.795), hospitalization days (p = 0.261), or adverse events (p = 0.554).

Conclusions: Using mitoxantrone or doxorubicin as induction therapy in newly diagnosed APL is a safe and adequate alternative with comparable outcomes to first-line agents in scenarios where the latter might not be readily available, such as in low-middle-income countries.