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Annals of Hematology Nov 2023Many sickle cell disease (SCD) patients lack matched family donors (MFD) or matched unrelated donors (MUD), implying haploidentical donors (MMFD) as a logical donor...
Many sickle cell disease (SCD) patients lack matched family donors (MFD) or matched unrelated donors (MUD), implying haploidentical donors (MMFD) as a logical donor choice. We used a reduced toxicity protocol for all donor types. We included 31 patients (2-22 years) with MFD (n = 15), MMFD (10), or MUD (6) HSCT and conditioning with alemtuzumab/ATG, thiotepa, fludarabine and treosulfan, and post-transplant cyclophosphamide for MMFD. After the initial six patients, treosulfan was replaced by targeted busulfan (AUC 65-75 ng*h/ml). After a median follow-up of 26 months (6-123), all patients are alive and off immunosuppression. Two MMFD patients experienced secondary graft failure with recurrence of SCD, both after treosulfan conditioning. Neither acute GVHD ≥ °III nor moderate/severe chronic GVHD was observed. The disease-free, severe GVHD-free survival was 100%, 100%, and 80% in the MFD, MUD, and MMFD groups, respectively (p = 0.106). There was a higher rate of virus reactivation in MMFD (100%) and MUD (83%) compared to MFD (40%; p = 0.005), but not of viral disease (20% vs 33% vs 13%; p = 0.576). Six patients had treosulfan-based conditioning, two of whom experienced graft failure (33%), compared to 0/25 (0%) after busulfan-based conditioning (p = 0.032). Donor chimerism was ≥ 80% in 28/31 patients (90%) at last follow-up. Reduced toxicity myeloablative conditioning resulted in excellent overall survival, negligible GVHD, and low toxicity among all donor groups in pediatric and young adult patients with SCD.
PubMed: 37726493
DOI: 10.1007/s00277-023-05447-4 -
Synapse (New York, N.Y.) Jun 2019Cancer survivorship has increased greatly as therapies have become more advanced and effective. Thus, we must now focus on improving the quality of life of patients...
Cancer survivorship has increased greatly as therapies have become more advanced and effective. Thus, we must now focus on improving the quality of life of patients after treatment. After chemotherapy, many patients experience chemotherapy-induced cognitive decline, indicating a need to investigate pathologies associated with this condition. In this study, we addressed cognitive impairment after thioTEPA treatment by assessing behavior and assaying cytokine production and the structure of dendrites in the hippocampus. Male mice were given three intraperitoneal injections of thioTEPA. Five weeks later, the mice underwent behavior testing, and brains were collected for Golgi staining and cytokine analysis. Behavior tests included y-maze and Morris water maze and licking behavioral task. Cytokines measured include: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-10, IL-12p70, MCP-1, TNF-α, GMCSF, and RANTES. We observed decreased memory retention in behavioral tasks. Also, dendritic arborization and length were decreased after chemotherapy treatment. Finally, thioTEPA decreased cytokine production in animals treated with chemotherapy, compared to saline-treated controls. Here, we used a mouse model to correlate the decreases in dendritic complexity and inflammatory cytokine production with cognitive impairment after chemotherapy.
Topics: Animals; Antineoplastic Agents, Alkylating; Brain; Cognition; Cognitive Dysfunction; Cytokines; Injections, Intraperitoneal; Male; Maze Learning; Mice; Mice, Inbred C57BL; Movement; Thiotepa
PubMed: 30586195
DOI: 10.1002/syn.22085 -
Cancer Apr 2005Intracranial meningiomas are common and comprise 20% of all primary brain tumors. Meningiomas infrequently metastasize; however, to the authors' knowledge there are...
BACKGROUND
Intracranial meningiomas are common and comprise 20% of all primary brain tumors. Meningiomas infrequently metastasize; however, to the authors' knowledge there are limited data regarding the spread of disease through cerebrospinal fluid (CSF).
METHODS
Eight of 200 consecutive patients (4%) with meningiomas manifested CSF dissemination. CSF cytology was positive in all patients, and neuroradiographic studies were consistent with CSF dissemination in eight patients. The patients (6 women and 2 men) ranged in age from 24-87 years (mean age, 52 years). All patients had undergone prior surgery (range, one to five surgeries; median, two surgeries), radiotherapy (involved-field radiotherapy in seven patients and stereotactic radiotherapy in six patients), and chemotherapy (hydroxyurea in eight patients). Multiple sites of metastases were seen in all patients and were both within the nervous system (subarachnoid or ventricular tumor: intracranial in eight patients, spinal cord in four patients) and extraneural (subcutaneous, cervical lymph nodes, orbit, or pulmonary in five patients). Treatment utilized both systemic chemotherapy (temozolomide in four patients, irinotecan in three patients, hydroxyurea in three patients, interferon-alpha in two patients, and doxorubicin plus ifosfamide in one patient) and intraventricular chemotherapy (liposomal cytosine arabinoside in seven patients, thiotepa in one patient, and busulfan in one patient).
RESULTS
Treatment-related toxicity was seen in eight patients, including chemical meningitis in eight patients (Grade 2), neutropenia in five patients (Grade 2 in four patients and Grade 3 in one patient), fatigue in one patient (Grade 2), and gastrointestinal toxicity in one patient (Grade 2). The best response was stable disease in seven patients and progressive disease in one patient. The response duration ranged from 2-31 months (median, 3.5 months). The median survival was 5.5 months, and 3 patients were alive with disease at the time of last follow-up.
CONCLUSIONS
The treatment of CSF-disseminated meningioma, although feasible and comparatively nontoxic, was associated with modest outcomes despite combined systemic and intraventricular chemotherapy.
Topics: Adult; Aged; Antineoplastic Agents; Brain Neoplasms; Central Nervous System Neoplasms; Cerebrospinal Fluid; Female; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Meningioma; Middle Aged; Skin Neoplasms; Spinal Cord Neoplasms
PubMed: 15690330
DOI: 10.1002/cncr.20926 -
Cancers Jan 2023Consolidation therapy has improved the outcome of newly diagnosed PCNSL patients. Whole-brain radiotherapy (WBRT) was the first consolidation strategy used and... (Review)
Review
BACKGROUND
Consolidation therapy has improved the outcome of newly diagnosed PCNSL patients. Whole-brain radiotherapy (WBRT) was the first consolidation strategy used and represented the gold standard for many years, but at the expense of a high risk of neurotoxicity. Thus, alternative strategies are being investigated in order to improve disease outcomes and to spare the neurocognitive side effects due to WBRT.
METHODS
We reviewed published studies on PCNSL patients treated with HDC/ASCT, focusing on the efficacy and safety of the conditioning regimens. Prospective and retrospective studies, published in the English language from 1992 to 2022, in high-quality international journals were identified in PubMed.
RESULTS
Consolidation with HDC containing highly CNS-penetrating agents (thiotepa, busulfan or BCNU) followed by ASCT provided long-term disease control and survival in PCNSL patients. Two prospective randomized studies, comparing HDC/ASCT versus WBRT, reported similar progression-free survival (PFS) and similar results on the decline in neurocognitive functions in a substantial proportion of patients after WBRT but not after HDC-ASCT. A recent randomized study comparing HDC/ASCT versus non-myeloablative consolidation reported a longer PFS in transplanted patients.
CONCLUSION
ASCT conditioned with regimens, including highly CNS-penetrating agents, represents, to date, the best choice among the available consolidation strategies for fit newly diagnosed PCNSL patients.
PubMed: 36672475
DOI: 10.3390/cancers15020526 -
Transplantation and Cellular Therapy Jul 2021One hundred and sixty-one patients underwent haploidentical stem cell transplantation (haploSCT) with thiotepa, busulfan, and fludarabine conditioning followed by...
Combining Three Different Pretransplantation Scores Improves Predictive Value in Patients after Haploidentical Stem Cell Transplantation with Thiotepa, Busulfan, and Fludarabine Conditioning and Post-Transplantation Cyclophosphamide.
One hundred and sixty-one patients underwent haploidentical stem cell transplantation (haploSCT) with thiotepa, busulfan, and fludarabine conditioning followed by post-transplantation cyclophosphamide (PTCy) (on days +3 and +4) and tacrolimus as graft-versus-host disease prophylaxis. Forty-two percent of patients had a high or very high revised Disease Risk Index (rDRI), 55% had an European Society for Blood and Marrow Transplantation risk score (EBMT-RS) ≥4, and 36% had an age-adjusted Hematopoietic Cell Transplant Comorbidity Index (HCT-CI-age) score ≥3. Each of these was considered an unfavorable score. Using the pretransplantation unfavorable scores that had an independent impact on each transplantation outcome studied in multivariate analysis allowed for better stratification of patient outcomes. Thus, the 3-year overall survival (OS) in patients with 0, 1, 2, and 3 unfavorable scores was 86%, 56%, 36%, and 24%, respectively. Nonrelapse mortality (NRM) was negatively impacted by the EBMT-RS and the HCT-CI-age score (3-year NRM in patients with 0, 1, and 2 unfavorable scores was 12%, 33%, and 43%, respectively), whereas the EBMT-RS and the rDRI had an impact on the 3-year relapse incidence (8%, 18%, and 41% in patients with 0, 1, and 2 unfavorable scores, respectively). In conclusion, our study shows that combining 2 or 3 of these well-defined pretransplantation scores improves the ability to predict transplantation outcomes in the setting of haploSCT with PTCy.
Topics: Busulfan; Cyclophosphamide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Thiotepa; Transplantation Conditioning; Vidarabine
PubMed: 33775908
DOI: 10.1016/j.jtct.2021.03.021 -
HemaSphere Oct 2023We conducted a registry analysis including adult acute myeloid leukemia (AML) patients in remission who had received thiotepa, busulfan, and fludarabine (TBF) or...
Thiotepa-busulfan-fludarabine Compared to Treosulfan-based Conditioning for Haploidentical Transplant With Posttransplant Cyclophosphamide in Patients With Acute Myeloid Leukemia in Remission: A Study From the Acute Leukemia Working Party of the EBMT.
We conducted a registry analysis including adult acute myeloid leukemia (AML) patients in remission who had received thiotepa, busulfan, and fludarabine (TBF) or treosulfan-based (Treo) conditioning for haplo-hematopoietic stem cell transplant (HSCT) with posttransplant cyclophosphamide (PTCy) between 2010 and 2020. A total of 1123 patients met the inclusion criteria (968 received TBF and 155 received Treo). A 1:1 matched-pair analysis was performed on 142 TBF and 142 Treo patients. In the Treo group, 68% of patients received treosulfan at a dose ≥36 g/m and 54% of patients received a second alkylator (thiotepa or melphalan). We observed a trend toward increased incidence of grade II-IV acute (a) graft-versus-host disease (GVHD) at 180 days in the TBF group compared with Treo (29% versus 20%; = 0.08), while incidence of grade III-IV aGVHD was not statistically different. Similarly, the incidence of chronic (c) GVHD was not statistically different in the 2 groups. Incidence of nonrelapse mortality at 2 years was 19% in TBF and 14% in Treo ( = 0.4). Relapse incidence at 2 years was not statistically different in the 2 groups (16% and 18% in TBF and Treo, respectively; = 0.9). Leukemia-free survival, overall survival, and GVHD-free, relapse-free survival was 65% versus 68% ( = 0.6), 73% versus 76% ( = 0.5), and 54% versus 53% ( = 0.8) in TBF versus Treo, respectively. In conclusion, we did not find a significant difference between the 2 conditioning in the present study; Treo and TBF represent 2 valid alternative regimens for haplo-HSCT with PTCy for AML in remission.
PubMed: 37746158
DOI: 10.1097/HS9.0000000000000952 -
The Cochrane Database of Systematic... Sep 2010The safety of conservative surgery and the benefit of additional interventions after surgery for borderline ovarian tumours are unknown. (Review)
Review
BACKGROUND
The safety of conservative surgery and the benefit of additional interventions after surgery for borderline ovarian tumours are unknown.
OBJECTIVES
To evaluate the benefits and harm of different treatment modalities offered for borderline ovarian tumours.
SEARCH STRATEGY
We searched the Cochrane Gynaecological Cancer Group Trials Register to 2009, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE and EMBASE to 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that compared different interventions in adult women diagnosed with borderline ovarian tumours of any histological variant.
DATA COLLECTION AND ANALYSIS
Two review authors independently abstracted data and assessed risk of bias.
MAIN RESULTS
We identified seven RCTs that enrolled 372 women. We could not pool results of trials as the treatment comparisons differed.Six RCTs (n = 340) conducted over 15 years ago, evaluated adjuvant therapy (chemotherapy, pelvic external irradiation or intra-peritoneal radioactive isotope therapy) after radical surgery; over 87% of participants had Stage I tumours. Most participants were followed up for over 10 years. Overall and recurrence-free survival were similar between both arms of these trials, except that one trial (n = 66) showed a significantly lower survival (P = 0.03) in women who received chemotherapy (thio-TEPA). Adverse effects of treatment were incompletely reported and all six trials were at high risk of bias.One further trial (n = 32) that recruited participants with bilateral serous tumours who were wishing fertility preservation, revealed a significantly increased chance of pregnancy (hazard ratio (HR) = 3.3, 95% CI 1.4 to 8.0) but non-significantly earlier disease recurrence (HR = 1.5, 95% CI 0.6 to 3.8) in the women who had ultra-conservative surgery (bilateral cystectomy) than in those who had conservative surgery (cystectomy and contralateral oophorectomy). This trial was at low risk of bias.Quality of life (QoL) was not documented in any included trial. We did not find any trials that compared radical with conservative surgery or laparoscopy with laparotomy.
AUTHORS' CONCLUSIONS
We did not find evidence to support the use of any specific type of adjuvant therapy for borderline ovarian tumours. RCTs evaluating the benefit of adjuvant therapy with optimally dosed chemotherapy and newer targeted drugs are necessary, particularly for advanced borderline ovarian tumours. The low mortality from borderline ovarian tumours should make recurrence-free survival, time to recurrence and morbidity important end points in such trials.Bilateral cystectomy may be offered to women with bilateral borderline ovarian tumours diagnosed intra-operatively who are wishing to preserve their fertility. Similarly, women who had RCTs comparing radical with conservative surgery and comparing laparoscopy with laparotomy are needed.
Topics: Adult; Chemotherapy, Adjuvant; Female; Humans; Neoplasm Staging; Ovarian Neoplasms; Pregnancy; Quality of Life; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic
PubMed: 20824864
DOI: 10.1002/14651858.CD007696.pub2 -
Frontiers in Oncology 2022Autologous stem cell transplantation (ASCT) remains the standard of care for patients with newly diagnosed multiple myeloma (MM). Several attempts to improve the...
Busulfan and thiotepa as a conditioning regimen for autologous stem cell transplantation in patients with multiple myeloma: A study of the Korean Multiple Myeloma Working Party (KMMWP-1801 study).
BACKGROUND
Autologous stem cell transplantation (ASCT) remains the standard of care for patients with newly diagnosed multiple myeloma (MM). Several attempts to improve the efficacy of conditioning regimens have been conducted in MM, but no more effective regimen than conventional high-dose melphalan has been introduced.
OBJECTIVE
In this study, the efficacy and toxicity of busulfan and thiotepa (BuTT) and those of high-dose melphalan (HD-MEL) were compared retrospectively as a conditioning regimen for ASCT in patients with MM.
STUDY DESIGN
Included in the analysis were 114 patients who received BuTT and 114 patients who received HD-MEL treatment between March 2008 and May 2020. The BuTT regimen consisted of intravenous thiotepa 5 mg/kg once a day from days 7 to 6, followed by intravenous busulfan 3.2 mg/kg once a day from days 5 to 3. The HD-MEL conditioning regimen consisted of melphalan 100 mg/m once a day from days 3 to 2.
RESULTS
The overall response rate after ASCT did not differ between BuTT and HD-MEL (94.7% in BuTT vs. 97.4% in HD-MEL, = 0.333). After a median follow-up of 47.6 months, progression-free survival (PFS) tended to be longer in the BuTT group (median PFS, 41.5 months vs. 30.3 months; hazard ratio (HR), 0.706; 95% confidence interval (CI), 0.497-1.004, = 0.053). In the subgroup analysis of patients who did not proceed to maintenance or consolidation treatment after ASCT, the difference in PFS became more significant (median PFS, 41.5 months vs. 24.4 months; HR, 0.621; 95% CI, 0.388-0.993; = 0.047). Additionally, the BuTT group had fewer adverse events, such as grade 3 or 4 stomatitis and diarrhea, than the HD-MEL group (stomatitis, 10.5% vs. 23.7%, = 0.013; diarrhea, 10.5% vs. 25.4%, = 0.005). There was no difference in the occurrence of venous-occlusive disease (2.6% in BuTT vs. 0.9% in HD-MEL, = 0.622).
CONCLUSION
Our study results suggest that BuTT is an effective alternative conditioning regimen with reduced toxicity in patients with newly diagnosed MM.
PubMed: 36110935
DOI: 10.3389/fonc.2022.959949 -
British Medical Journal Jan 1963
Topics: Breast Neoplasms; Female; Humans; Ovary; Testosterone; Thiotepa
PubMed: 13984345
DOI: 10.1136/bmj.1.5322.54-a -
Blood Advances Jan 2024Allogeneic hematopoietic stem cell transplantation (HSCT) is highly effective for treating pediatric high-risk or relapsed acute lymphoblastic leukemia (ALL). For young...
Allogeneic hematopoietic stem cell transplantation (HSCT) is highly effective for treating pediatric high-risk or relapsed acute lymphoblastic leukemia (ALL). For young children, total body irradiation (TBI) is associated with severe late sequelae. In the FORUM study (NCT01949129), we assessed safety, event-free survival (EFS), and overall survival (OS) of 2 TBI-free conditioning regimens in children aged <4 years with ALL. Patients received fludarabine (Flu), thiotepa (Thio), and either busulfan (Bu) or treosulfan (Treo) before HSCT. From 2013 to 2021, 191 children received transplantation and were observed for ≥6 months (median follow-up: 3 years). The 3-year OS was 0.63 (95% confidence interval [95% CI], 0.52-0.72) and 0.76 (95% CI, 0.64-0.84) for Flu/Thio/Bu and Flu/Thio/Treo (P = .075), respectively. Three-year EFS was 0.52 (95% CI, 0.41-0.61) and 0.51 (95% CI, 0.39-0.62), respectively (P = .794). Cumulative incidence of nonrelapse mortality (NRM) and relapse at 3 years were 0.06 (95% CI, 0.02-0.12) vs 0.03 (95% CI: <0.01-0.09) (P = .406) and 0.42 (95% CI, 0.31-0.52) vs 0.45 (95% CI, 0.34-0.56) (P = .920), respectively. Grade >1 acute graft-versus-host disease (GVHD) occurred in 29% of patients receiving Flu/Thio/Bu and 17% of those receiving Flu/Thio/Treo (P = .049), whereas grade 3/4 occurred in 10% and 9%, respectively (P = .813). The 3-year incidence of chronic GVHD was 0.07 (95% CI, 0.03-0.13) vs 0.05 (95% CI, 0.02-0.11), respectively (P = .518). In conclusion, both chemotherapeutic conditioning regimens were well tolerated and NRM was low. However, relapse was the major cause of treatment failure. This trial was registered at www.clinicaltrials.gov as #NCT01949129.
Topics: Child; Child, Preschool; Humans; Busulfan; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Thiotepa; Transplantation Conditioning
PubMed: 37738088
DOI: 10.1182/bloodadvances.2023010591