Regimen For Stem Cell Transplantation Research Articles

Superior Survival After Unrelated Allogeneic Stem Cell Transplantation With Low-Dose ATG Compared to Low-Dose TBI in Myeloablative Fludarabine/Busulfan-Based Regimen for MDS on Behalf of the Adult MDS Working Group of the JSTCT

The fludarabine/intravenous busulfan 12.8 mg/kg (FB4) regimen is an effective conditioning regimen in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome (MDS); however, limited data is available on the prognostic impact of FB4 with low-dose anti-thymoglobulin (ATG ≤ 5 mg/kg) or low-dose total body irradiation (TBI ≤ 4 Gy). Therefore, we retrospectively evaluated the outcomes in 280 adults with de novo MDS who underwent their first transplantation from an unrelated donor between 2009 and 2018. Median age was 61 years (range, 16 to 70 years). In the FB4 alone (FB4), FB4 plus ATG (FB4-ATG), and FB4 plus TBI (FB4-TBI) groups, 3-years overall survival (OS) rates were 39.9%, 64.8%, and 43.7%; 3-years nonrelapse mortality (NRM) were 32.1%, 22.1%, and 27.1%; and 3-years relapse incidences were 34.7%, 21.2%, and 28.9%, respectively. The multivariate analyses showed that FB4-ATG group significantly correlated with better OS (hazard Ratio [HR], 0.51; 95% confidence interval [CI], 0.27 to 0.95; P = .032) than FB4 group. FB4-ATG group tended to correlate with lower NRM (HR, 0.36; 95% CI, 0.13 to 1.06; P = .063) than FB4 group. In comparison with FB4-TBI group, FB4-ATG group showed better OS (HR 0.52, 95% CI 0.27 to 0.99, P = .049) and NRM (HR 0.034, 95% CI 0.11 to 0.92, P = .034). No significant differences were observed in OS and NRM between the FB4-TBI and FB4 groups. The present study demonstrated that the FB4 plus low-dose ATG regimen improved OS and NRM, but FB4 plus low-dose TBI regimen had no clear benefit over FB4 alone, in MDS patients who used unrelated donors.

BEAM or cyclophosphamide in autologous haematopoietic stem cell transplantation for relapsing-remitting multiple sclerosis

The most widely used conditioning regimens in autologous haematopoietic stem cell transplantation (ASCT) for multiple sclerosis (MS) are BEAM with anti-thymocyte globulin (ATG) and high-dose cyclophosphamide with ATG (Cy/ATG). In this retrospective study, we compare efficacy and safety of these regimens when used for relapsing-remitting MS. We assessed 231 patients treated in Sweden before January 1, 2020. The final cohort comprised 33 patients treated with BEAM/ATG and 141 with Cy/ATG. Prospectively collected data from the Swedish MS registry were used for efficacy, and electronic health records for procedure-related safety. The Kaplan–Meier estimate of ‘no evidence of disease activity’ (NEDA) at 5 years was 81% (CI 68–96%) with BEAM/ATG and 71% (CI 63–80%) with Cy/ATG, p = 0.29. Severe adverse events were more common with BEAM/ATG, mean 3.1 vs 1.4 per patient, p = <0.001. Febrile neutropaenia occurred in 88% of BEAM/ATG patients and 68% of Cy/ATG patients, p = 0.023. Average hospitalisation was 3.0 days longer in BEAM/ATG patients from day of stem-cell infusion, p < 0.001. While both regimens showed similar efficacy, BEAM/ATG was associated with more severe adverse events and prolonged hospitalisation. In the absence of randomised controlled trials, Cy/ATG may be preferable for ASCT in patients with relapsing-remitting MS due to its favourable safety profile.

Targeting CDC42 reduces skeletal degeneration after hematopoietic stem cell transplantation

AbstractOsteopenia and osteoporosis are common long-term complications of the cytotoxic conditioning regimen for hematopoietic stem cell transplantation (HSCT). We examined mesenchymal stem and progenitor cells (MSPCs), which include skeletal progenitors, from mice undergoing HSCT. Such MSPCs showed reduced fibroblastic colony-forming units frequency, increased DNA damage, and enhanced occurrence of cellular senescence, whereas there was a reduced bone volume in animals that underwent HSCT. This reduced MSPC function correlated with elevated activation of the small Rho guanosine triphosphate hydrolase CDC42, disorganized F-actin distribution, mitochondrial abnormalities, and impaired mitophagy in MSPCs. Changes and defects similar to those in mice were also observed in MSPCs from humans undergoing HSCT. A pharmacological treatment that attenuated the elevated activation of CDC42 restored F-actin fiber alignment, mitochondrial function, and mitophagy in MSPCs in vitro. Finally, targeting CDC42 activity in vivo in animals undergoing transplants improved MSPC quality to increase both bone volume and trabecular bone thickness. Our study shows that attenuation of CDC42 activity is sufficient to attenuate reduced function of MSPCs in a BM transplant setting.

Efficacy of a Modified Post-Transplant Cyclophosphamide Regimen for Unrelated Donor Hematopoietic Stem Cell Transplantation in Patients with Severe Aplastic Anemia: A Prospective Study

The aim of the present study was to examine the efficacy of the modified post-transplant cyclophosphamide (PTCy) regimen, which involved reducing the Cy dose to 40 mg on days +3 and +4 in patients with severe aplastic anemia (SAA) subjected to unrelated donor allogeneic hematopoietic stem cell transplantation (URD-HSCT). For this purpose, a prospective single-center trial was conducted and the clinical outcomes were collected from 30 patients with SAA treated with the modified PTCy regimen for URD-HSCT. The median time to neutrophil and platelet engraftment was 13 days (range, 11 to 16) and 12 days (range, 5 to 33), respectively. The cumulative incidence of neutrophil and platelet engraftment was 93.1% ± 0.3% and 96.6% ± 0.2%, respectively. The 2-year overall survival (OS) was 97% (95% confidence interval [CI]: 90%-100%] and 2-year graft-versus-host disease (GVHD) and rejection-free survival (GRFS) was 93% (95% CI: 85%-100%). The incidence rates of acute GVHD (aGVHD) and chronic GVHD (cGVHD) were 13.8 ± 0.4% and 10.3 ± 0.3%, respectively, and no patients developed grades III-IV aGVHD. However, only one patient developed a moderate extensive cGVHD. The incidence of reconstitution varies among different subsets of immune cells after URD-HSCT. Natural killer (NK) cells recover first, followed by CD8+ T and CD19+ B cells, and finally CD4+ T cells. In conclusion, the present study demonstrates that the modified PTCy regimen, with a reduced dose of 40 mg on days +3 and +4, may be an effective regimen for URD-HSCT in patients with SAA and reduce the occurrence of the GVHD.

Cyclophosphamide and horse anti-thymocyte globulin versus fludarabine, reduced cyclophosphamide and rabbit anti-thymocyte globulin conditioning regimen for allogeneic hematopoietic stem cell transplantation from matched sibling donors in patients with acquired aplastic anemia

ABSTRACT Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acquired aplastic anemia (acquired AA) in young patients. The objective of the study was to compare patient outcomes after Cyclophosphamide and horse antithymocyte globulin (Cy-hATG) versus Fludarabine-cyclophosphamide and rabbit ATG (Flu-Cy-rATG) as part of conditioning regimen in allo-HSCT for acquired AA. Research design and methods Descriptive retrospective study conducted on patients with acquired AA who received allo-HSCT from HLA-matched sibling donors between January 2008 and August 2022 after conditioning regimen with Cy-hATG or Flu-Cy-rATG. Results A total of 121 patients were enrolled. Cumulative incidence of graft failure was 11.2% in Cy-hATG and 5.3% Flu-Cy-rATG group. There were no significant differences between the two groups in terms of acute GVHD, chronic GVHD, and transplant related mortality. Flu-Cy-rATG group was associated with significantly higher CMV and EBV reactivation(s) compared to Cy-hATG group (p = 0.008 and 0.035, respectively). After a median follow-up of 58 months, estimated overall survival, event-free survival, and graft rejection-free survival were not statistically different between the two groups. Conclusions In high-risk population, Flu-Cy-rATG is associated with comparable outcomes to Cy-hATG in allo-HSCT from MSD. However, it seems to be associated with significant risk of viral infections.

Evaluate the Efficacy of Myeloablative Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myelogenous Leukemia at BTH, Vietnam.

Background: Busulfan plus cyclophosphamide (Bu/Cy) is considered one of the classical myeloablative conditioning regimens. However, its toxicity can significantly increase mortality rates. To reduce both acute and long-term complications after hematopoietic stem cell transplantation (HSCT), newer conditioning regimens are being investigated. The purposes of this study were to assess the efficacy and safety of busulfan plus cyclophosphamide (Bu/Cy) and busulfan plus fludarabine (Bu/Flu) conditioning regimen for allogeneic HSCT (allo-HSCT) in acute myelogenous leukemia (AML). Materials and Methods: We conducted a single-center, retrospective analysis of AML, both adults and children, who underwent either Bu/Cy or Bu/Flu conditioning regimen for allo-HSCT and received peripheral blood stem cell transplants from HLA-matched donors. Results: From 2005 - 2019, 49 AML patients receiving Bu/Cy and 21 receiving Bu/Flu were identified, meeting inclusion criteria. The two groups showed no significant differences in age, gender, disease status pre-transplant, the median time to neutrophil and platelet engraftment. Bu/Flu patients had a shorter duration of neutropenia (median 7 days vs 10 days, p = 0.001) and shorter duration of thrombocytopenia (median 10 days vs 15 days, p = 0.016) than Bu/Cy. No difference was observed in disease-free survival (DFS) and overall survival (OS) between the two groups. Both univariate and multivariate analyses showed that age, disease status pre-transplant, and chronic graft-versus-host disease (GvHD) are related to worse DFS and OS. Conclusion : With similar efficacy to Bu/Cy but faster neutrophil and platelet recovery time, Bu/Flu is suitable as a pre-HSCT conditioning regimen for patients with AML.

Fludarabine, busulfan, and melphalan conditioning regimen in allogeneic hematopoietic stem cell transplantation for adult patients with myeloid malignancies: A multicenter retrospective study.

Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo-HSCT following fludarabine(≥100mg/m2), busulfan (≥3.2mg/kg) and melphalan (≥100mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n=171, MDS-IB-1 or 2 n=44, CMML n=6) with median age of 46 were enrolled in this study. The median follow-up was 507 days for survivors. The 2-year NRM, CIR, OS and DFS were 10.6%±2.2%, 14.8%±3.3%, 79.4%±3.7% and 74.6%±3.7%, respectively. In multivariate analyses, high HCT-CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p=0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p=0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p=0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR=7.92, 95%CI 1.05-60.03, p=0.045; HR=3.64, 95%CI 1.40-9.44, p=0.008; respectively), while post-transplantation cyclophosphamide based graft-versus-host disease prophylaxis was associated with lower CIR (HR=0.24 95%CI 0.11-0.54, p=0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.

Fludarabine-induced bradycardia in allogeneic hematopoietic stem cell transplantation: A retrospective study.

Fludarabine, a purine analog, is getting more attention with the increasing use of reduced intensive conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The side effect of bradycardia was observed in only a few cases reported in the literature. In clinical practice, bradycardia can be asymptomatic or cause syncope and cardiac arrest. This study aimed to evaluate the bradycardia side effect of fludarabine used in the conditioning regimen in allo-HSCT recipients and to increase awareness of this issue. This retrospective study included 73 patients who received fludarabine in the allo-HSCT conditioning regimen between January 2015 and January 2021. Patients with and without bradycardia were compared regarding demographic data, allo-HSCT characteristics, electrolyte values, fludarabine administration dose and duration, and survival. Univariate and multivariate analyzes were performed to evaluate independent predictors for fludarabine-induced bradycardia. Fludarabine administration doses and days were higher in the bradycardia group, but no statistically significant difference was observed. In the multivariate analysis, age was the only independent predictor of fludarabine-induced bradycardia (odds ratio (OR) 0.93, 95% confidence interval (CI): 0.89-0.98, p = 0.007). The median age in the group with bradycardia was 19 years younger than those without bradycardia (34 (19-49) vs 53 (19-69), p = 0.005). In 11 (84.6%) of the patients who had bradycardia, bradycardia improved with the discontinuation of fludarabine alone, but atropine was administered in 2 (15.4%) patients. Age was the only independent predictor of fludarabine-induced bradycardia; therefore, close heart rate monitoring is recommended during fludarabine administration, especially in younger patients.

BeEAM vs. BEAM: evaluating conditioning regimens for autologous stem cell transplantation in patients with relapsed or refractory DLBCL.

To evaluate whether BeEAM is an alternative to BEAM for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Data of 60 patients with relapsed or refractory DLBCL who underwent ASCT from January 2018 to June 2023 in our center, including 30 patients in the BeEAM group and 30 patients in the BEAM group, were retrospectively analyzed. The time to hematopoietic reconstitution, treatment-related adverse events, number of hospitalization days, hospitalization cost, and survival benefit were compared between the two groups. The clinical characteristics of the patients did not significantly differ between the two groups. The median number of reinfused CD34 + cells was 5.06 × 106/kg and 5.17 × 106/kg in the BeEAM and BEAM groups, respectively, which did not significantly different (p = 0.8829). In the BeEAM and BEAM groups, the median time to neutrophil implantation was 10.2 and 10.27 days, respectively (p = 0.8253), and the median time to platelet implantation was 13.23 and 12.87 days, respectively (p = 0.7671). In the BeEAM and BEAM groups, the median hospitalization duration was 30.37 and 30.57 days, respectively (p = 0.9060), and the median hospitalization cost was RMB 83,425 and RMB 96,235, respectively (p = 0.0560). The hospitalization cost was lower in the BeEAM group. The most common hematologic adverse events were grade ≥ 3 neutropenia and thrombocytopenia, whose incidences were similar in the two groups. The most common non-hematologic adverse events were ≤ grade 2 and the incidences of these events did not significantly differ between the two groups. Median overall survival was not reached in either group, with predicted 5-year overall survival of 72.5% and 60% in the BeEAM and BEAM groups, respectively (p = 0.5872). Five-year progression-free survival was 25% and 20% in the BeEAM and BEAM groups, respectively (p = 0.6804). As a conditioning regimen for relapsed or refractory DLBCL, BeEAM has a desirable safety profile and is well tolerated, and its hematopoietic reconstitution time, number of hospitalization days, and survival benefit are not inferior to those of BEAM. BeEAM has a lower hospitalization cost and is an alternative to BEAM.

Total body irradiation versus thiotepa/busulfan-based conditioning regimens for myeloablative allogeneic stem cell transplantation in adults with acute lymphoblastic leukemia.

Total body irradiation (TBI)-based conditioning regimens are generally recommended for allogeneic HSCT (allo-HSCT) in patients with acute lymphoblastic leukemia (ALL). Recent evidence suggests that modern chemotherapy-based regimens may be as effective. This multicenter retrospective study compared the clinical outcomes of myeloablative allo-HSCT with thiotepa, busulfan, and cyclophosphamide/fludarabine (TTB) to TBI-based conditioning. Between 2002 to 2018, 63 and 114 patients received TTB- and TBI-based conditioning regimens, respectively. The 5-year cumulative incidence of relapse was lower in the TBI cohort compared to the TTB cohort (30% [95% CI, 22-38] versus 47% [95% CI, 36-59]; P = 0.03). Multivariate analysis identified T-ALL, Ph-negative B-ALL, and measurable residual disease associated with a higher relapse risk. The 5-year cumulative incidence of non-relapsed mortality (NRM) was significantly lower with TTB (12% [95% CI, 5-20]) compared to TBI (25% [95% CI, 18-33]) (P = 0.001). Multivariate analysis found TBI conditioning, older age, and advanced stages of ALL at transplantation associated with a higher NRM. No statistical difference was seen in overall survival (49% [95% CI, 40-58] and 46% [95% CI, 35-60]) in the TBI and TTB groups, respectively; P = 0.9). The study suggests that TTB-based conditioning may be a promising option for ALL patients undergoing allo-HSCT, as it resulted in similar OS and lower NRM than TBI-based conditioning.

Deep learning-based optimization of field geometry for total marrow irradiation delivered with volumetric modulated arc therapy.

Total marrow (lymphoid) irradiation (TMI/TMLI) is a radiotherapy treatment used to selectively target the bone marrow and lymph nodes in conditioning regimens for allogeneic hematopoietic stem cell transplantation. A complex field geometry is needed to cover the large planning target volume (PTV) of TMI/TMLI with volumetric modulated arc therapy (VMAT). Five isocenters and ten overlapping fields are needed for the upper body, while, for patients with large anatomical conformation, two specific isocenters are placed on the arms. The creation of a field geometry is clinically challenging and is performed by a medical physicist (MP) specialized in TMI/TMLI. To develop convolutional neural networks (CNNs) for automatically generating the field geometry of TMI/TMLI. The dataset comprised 117 patients treated with TMI/TMLI between 2011 and 2023 at our Institute. The CNN input image consisted of three channels, obtained by projecting along the sagittal plane: (1) average CT pixel intensity within the PTV; (2) PTV mask; (3) brain, lungs, liver, bowel, and bladder masks. This "averaged" frontal view combined the information analyzed by the MP when setting the field geometry in the treatment planning system (TPS). Two CNNs were trained to predict the isocenters coordinates and jaws apertures for patients with (CNN-1) and without (CNN-2) isocenters on the arms. Local optimization methods were used to refine the models output based on the anatomy of the patient. Model evaluation was performed on a test set of 15 patients in two ways: (1) by computing the root mean squared error (RMSE) between the CNN output and ground truth; (2) with a qualitative assessment of manual and generated field geometries-scale: 1=not adequate, 4=adequate-carried out in blind mode by three MPs with different expertise in TMI/TMLI. The Wilcoxon signed-rank test was used to evaluate the independence of the given scores between manual and generated configurations (p<0.05 significant). The average and standard deviation values of RMSE for CNN-1 and CNN-2 before/after local optimization were 15±2/13±3mm and 16±2/18±4mm, respectively. The CNNs were integrated into a planning automation software for TMI/TMLI such that the MPs could analyze in detail the proposed field geometries directly in the TPS. The selection of the CNN model to create the field geometry was based on the PTV width to approximate the decision process of an experienced MP and provide a single option of field configuration. We found no significant differences between the manual and generated field geometries for any MP, with median values of 4versus 4 (p=0.92), 3versus 3 (p=0.78), 4versus 3 (p=0.48), respectively. Starting from October 2023, the generated field geometry has been introduced in our clinical practice for prospective patients. The generated field geometries were clinically acceptable and adequate, even for an MP with high level of expertise in TMI/TMLI. Incorporating the knowledge of the MPs into the development cycle was crucial for optimizing the models, especially in this scenario with limited data.

Impact of prophylactic echinocandin on the development of neurological complications in patients receiving busulfan-containing conditioning regimens for stem cell transplantation: A single-center retrospective study.

Although neurotoxicity is a major adverse event associated with busulfan, little information is available regarding the association between drug interactions and neurological symptoms during busulfan-based regimens. This study evaluated the association between prophylactic echinocandins and neurological complications in patients receiving busulfan-containing conditioning regimens for stem cell transplantation. We retrospectively included consecutive patients who administered intravenous busulfan as a conditioning regimen at our facility between 2007 and 2022. Prophylactic echinocandin use was defined as the use of an echinocandin antifungal drug to prevent invasive fungal disease in SCT recipients. The primary outcome was the incidence of neurological complications within 7 days of busulfan initiation and was compared between the echinocandin group (patients received prophylactic echinocandin) and nonechinocandin group (patients received prophylactic antifungal drugs other than echinocandin and those without antifungal prophylaxis). Among the 59 patients included in this study, the incidence of neurological complications in the echinocandin (n = 26) and nonechinocandin groups (n = 33) was 30.8% and 63.6%, respectively. We observed a negative association between prophylactic echinocandin use and the development of neurological complications after adjusting for the propensity score for receiving prophylactic echinocandins (adjusted odds ratio 0.294, 95% confidence interval 0.090 to 0.959). We observed a lower incidence of neurological complications in the echinocandin group than in the nonechinocandin group. Our results suggested that the choice of antifungal prophylaxis is associated with busulfan neurotoxicity.

High dose total marrow irradiation (TMI) does not increase long-term toxicity of myeloablative fludarabine/busulfan (FluBu4) conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT).

Based on a previous phase 1 study, total marrow irradiation (TMI) at 9Gy was added to a myeloablative FluBu4 conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for myeloid malignancies. Here, we report on the long-term toxicity of TMI combined with FluBu4 and compare it to patients who received only FluBu4. We retrospectively analyzed 38 consecutive patients conditioned with FluBu4/TMI (n = 15) or FluBu4 (n = 23, control group) who had at least 1 year follow-up post-transplant. The rate of long-term adverse events that have been previously associated with total body irradiation (TBI) was analyzed in the two groups. The baseline characteristics did not differ between the two groups. The control group had a longer median follow-up (71.2 mo) than the TMI group (38.5 mo) (p = .004). The most common adverse events were xerostomia, dental complications, cataracts, or osteopenia and did not differ between the two groups. Cognitive dysfunction or noninfectious pneumonitis, often detected after high dose TBI, were also not different in the two groups (p = .12 and p = .7, respectively). There was no grade 4 adverse event. Our results suggest that a conditioning regimen with TMI 9Gy and FluBu4 does not increase long-term adverse events after allogeneic HSCT.

Long term outcomes of nonmyeloablative allogeneic stem cell transplantation with TSEB TLI and ATG for Mycosis Fungoides and Sezary Syndrome

Advanced stage (IIB-IVB) Mycosis Fungoides (MF) and Sezary Syndrome (SS) have a poor prognosis with median survival <5 years. We report long-term outcomes of a non-myeloablative allogeneic stem cell transplantation regimen consisting of total skin electron beam therapy, total lymphoid irradiation and antithymocyte globulin. Our prospective cohort consisted of 41 patients with a higher proportion of MF (34MF, 7SS). Acute GVHD Grade 2 to 4 was seen in 31.7% and chronic GVHD Grade 2 to 4 in 24%. The cumulative incidence of non-relapse mortality was 9.8% at 1 year and 12.6% at 2 years. At Day +90 post-transplant 66% of patients had a complete response (CR). With a median post-transplant follow up of 5.27 years, the 5-year overall survival rate was 37.7% (MF 36.7%, SS 57.1%). The 5-year cumulative incidence of progressive disease or relapse was 52.7% in all patients but only 20.8% in those with CR at transplant compared to 70.6% in those not in CR at transplant (p = 0.006). Long term survival is possible in advanced MF and SS with non-myeloablative transplantation and outcomes are improved in patients with CR at transplant.

Maintain Efficacy and Spare Toxicity: Traditional and New Radiation-Based Conditioning Regimens in Hematopoietic Stem Cell Transplantation.

Novelty in total body irradiation (TBI) as part of pre-transplant conditioning regimens lacked until recently, despite the developments in the field of allogeneic stem cell transplants. Long-term toxicities have been one of the major concerns associated with TBI in this setting, although the impact of TBI is not so easy to discriminate from that of chemotherapy, especially in the adult population. More recently, lower-intensity TBI and different approaches to irradiation (namely, total marrow irradiation, TMI, and total marrow and lymphoid irradiation, TMLI) were implemented to keep the benefits of irradiation and limit potential harm. TMI/TMLI is an alternative to TBI that delivers more selective irradiation, with healthy tissues being better spared and the control of the radiation dose delivery. In this review, we discussed the potential radiation-associated long-term toxicities and their management, summarized the evidence regarding the current indications of traditional TBI, and focused on the technological advances in radiotherapy that have resulted in the development of TMLI. Finally, considering the most recent published trials, we postulate how the role of radiotherapy in the setting of allografting might change in the future.

Clofarabine and High-Dose Melphalan Reduced Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation

Clofarabine and High-Dose Melphalan Reduced Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation

Busulfan with 400 centigray of total body irradiation and higher dose fludarabine: An alternative regimen for hematopoietic stem cell transplantation in pediatric acute lymphoblastic leukemia.

Hematopoietic stem cell transplantation can be curative for children with difficult-to-treat leukemia. The conditioning regimen utilized is known to influence outcomes. We report outcomes of the conditioning regimen used at the Alberta Children's Hospital, consisting of busulfan (with pharmacokinetic target of 3750μmol*min/L/day ±10%) for 4days, higher dose (250mg/m2 ) fludarabine and 400centigray (cGy) of total body irradiation. This retrospective study involved children receiving transplant for acute lymphoblastic leukemia (ALL). It compared children who fell within the target range for busulfan with those who were either not measured or were measured and fell outside this range. All other treatment factors were identical. Twenty-nine children (17 within target) were evaluated. All subjects engrafted neutrophils with a median [interquartile range] time of 14days [8-30days]. The cumulative incidence of acute graft-versus-host disease was 44.8% [95% confidence interval, CI: 35.6%-54.0%], while chronic graft-versus-host disease was noted in 16.0% [95% CI: 8.7%-23.3%]. At 2years, the overall survival was 78.1% [95% CI: 70.8%-86.4%] and event-free survival was 74.7% [95% CI: 66.4%-83.0%]. Cumulative incidence of relapse was 11.3% [95% CI: 5.1%-17.5%]. There were no statistically significant differences in between the group that received targeted busulfan compared with the untargeted group. Our conditioning regiment for children with ALL resulted in outcomes comparable to standard treatment with acceptable toxicities and significant reduction in radiation dose. Targeting busulfan dose in this cohort did not result in improved outcomes.

Evolution of dosimetric treatment planning for pediatric total lymphoid irradiation (TLI): a single-institution experience.

Total lymphoid irradiation (TLI) is a conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) which may reduce long-term toxicities attributed to other techniques, such as total body irradiation (TBI). At our institution, TLI treatments were first planned with the three-dimensional conformal radiation therapy (3D-CRT) technique and later with volumetric modulated arc therapy (VMAT). With the recent availability of a basic helical tomotherapy (HT), the possible dosimetric gain of the latter for TLI is studied. 22 pediatric patients were planned for VMAT and HT, prescribed to 8 Gy in 4 fractions. VMAT was planned with template based on a single cost function, using the Monaco treatment planning system (TPS). HT plans were planned using Accuray Precision TPS for a basic HT without the dynamic jaws feature or VOLO-Ultra algorithm. Plan quality was analyzed based on four quality indices, mean and maximum doses to planning target volume (PTV) and organs at risk (OARs), dose gradient and integral doses. Differences were analyzed with Wilcoxon signed-rank test. HT plans resulted in improved conformity (CI) and homogeneity indices (HI) (p < 0.05) but less steep dose gradient (p = 0.181). VMAT plans created larger areas with high doses within the PTV, while comparable doses to OARs, except mainly for the spinal marrow, for which a reduction of 37.7% in D2% was obtained (p < 0.05). Integral dose for non-tumor tissue was 11.3% lower with the VMAT template (p < 0.05). HT achieves better conformity and homogeneity even without its more advanced features. Nevertheless, the VMAT template achieves dosimetric results close to those of HT, both with similar clinical outcome.

Effect of exercise interventions on hospital length of stay and admissions during cancer treatment: a systematic review and meta-analysis

ObjectiveTo assess the effect of participating in an exercise intervention compared with no exercise during cancer treatment on the duration and frequency of hospital admissions.DesignSystematic review and meta-analysis.Data sourcesMEDLINE, EMBASE,...

Evaluation of busulfan, cyclophosphamide, and etoposide as a preparation regimen for autologous stem cell transplantation in Hodgkin’s lymphoma patients

Abstract: BACKGROUND: Hodgkin’s lymphoma (HL) exhibits a cure rate of 90% in patients diagnosed at an early stage and a cure rate ranging from 70% to 90% in patients diagnosed at an advanced stage. In the case of patients with relapsed/refractory HL (r/rHL), it is recommended to provide salvage chemotherapy initially, followed by autologous stem cell transplantation (ASCT). The ideal conditioning regimen for the transplantation process is still being investigated. OBJECTIVES: For individuals with r/rHL, high-dose chemotherapy combined with ASCT (HD-ASCT) is thought to be the most effective method of treatment. The purpose of this research was to evaluate the effectiveness and safety of the busulfan, cyclophosphamide, and etoposide (BuCyE) preparation regimen in r/rHL patients. MATERIALS AND METHODS: Retrospective analysis was conducted on the data of 67 lymphoma patients older than 18 years who had HD-ASCT with the BuCyE conditioning regimen between September 2014 and November 2021 (86 months). The research consisted of 34 r/r HL patients among them. A parenteral regimen of 0.8 mg/kg of busulfan every 6 h from day −7 to day −5, 50 mg/kg of cyclophosphamide on days −3 and −2, and 400 mg/m2 of etoposide on days −5 and −4 comprised the patient preparation regimen before ASCT. All data were collected from inpatient files and the Inonu University Turgut Ozal Medical Center Hospital Information System. RESULTS: The median age of the patients was 43 years, and 67.6% were males. The most common type of HL was nodular sclerosis, which was followed by mixed cellularity. The median time for platelet and neutrophil engraftment was 14 and 11 days, respectively. 5.0 × 106/kg was the median transplanted dose of CD34+ cells (2.1–13.55). Liver toxicity was observed in 6 (17.6%) patients. Eight patients suffered from pulmonary side effects. The median number of previous chemotherapies was 2 (2–4). In all lymphoma patients, the complete response rate was 61.8% (n = 21), whereas the disease progression rate was 32.3% (n = 11). Transplantation-related mortality on the 100th day was 8.8% (n = 3). Three-year overall survival was 57.17%. CONCLUSION: When the literature was reviewed, the studies with the BuCyE preparation regimen in patients with r/rHL were limited. This conditioning regimen was found to have fewer side effects and a lower cost. It can be preferable when compared to carmustine (BCNU), etoposide, cytarabine (ARA-C), and melphalan (known as BEAM) in r/rHL.