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We assessed the outcomes associated with thiotepa, busulfan and fludarabine (TBF) conditioning regimen in a cohort of 29 consecutive patients allografted for myelofibrosis (MF). The median age was 56 (range 42–70) years. According to the refined Dynamic International Prognostic Scoring System (DIPSS-plus), 15 (52%) patients were classified as high risk. Graft source was peripheral blood stem cells in 27 patients. Donor type was HLA-matched related (n = 5), matched unrelated (n = 16), mismatched unrelated (n = 1), and haploidentical (n = 7). All but 2 patients engrafted. The cumulative incidence (CI) of grade II–IV acute graft-versus-host disease (GVHD) was 21% (95% CI, 10–42) at day 100. The CI of chronic GVHD was 39% (95% CI, 23–65) at 3 years. The median follow-up period was 39 (range 14–60) months. Overall survival was 69% (95% CI, 50–83) at 3 years. No relapse was observed. TBF is a valid conditioning strategy in patients with MF. [ABSTRACT FROM AUTHOR]

Although the survival rates are extremely low for patients with secondary central nervous system lymphoma (SCNSL) treated with conventional chemotherapy and radiotherapy, more encouraging outcomes have recently been reported in small series with high-dose (HD) therapy and autologous stem cell transplant (ASCT). The optimal HD regimen for SCNSL is unknown. Despite reports of thiotepa/busulfan-based conditioning for primary CNS lymphoma, very little data exist regarding the use of this regimen for SCNSL. We analyzed 23 patients with SCNSL (median age 62 years) who underwent ASCT at two Alberta centers using thiotepa, busulfan, cyclophosphamide (TBC) in six patients prior to 2011 and rituximab-busulfan, melphalan, thiotepa (R-BuMelTt) in 17 patients after 2011. At a median follow-up of 27.8 months (4.2-113.6), the 2-year actuarial rate of progression-free survival was 76.1%. In conclusion, our results demonstrate encouraging survival outcomes for patients with SCNSL treated with R-BuMelTt and ASCT. [ABSTRACT FROM AUTHOR]

High-dose therapy with autologous stem cell transplant (autoSCT) is standard therapy for relapsed/refractory Hodgkin lymphoma, although the optimal conditioning regimen remains uncertain. We conducted a retrospective analysis of 100 consecutive patients with relapsed/refractory Hodgkin lymphoma who underwent autoSCT between 1998 and 2009. There were 60 patients who received busulfan, melphalan and thiotepa (BuMelTt) conditioning and 40 who received other common regimens. There were no significant differences in patient characteristics between the two groups. With a median follow-up of 4.3 years, the 5-year overall survival (OS) was superior for patients who received BuMelTt versus other conditioning (73% vs. 44%, p = 0.05). BuMelTt was also associated with an improved 5-year progression-free survival (66% vs. 37%, p = 0.03). There were no differences in length of hospitalization, febrile neutropenia, hepatic veno-occlusive disease or 100-day non-relapse mortality (NRM). There were more cases of severe mucositis but fewer episodes of bacteremia with BuMelTt. Our results suggest that BuMelTt may be a superior conditioning regimen for autoSCT in Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

We compared the tolerability and anti-myeloma effect of two conditioning regimens for autologous stem cell transplant (auto-SCT) in consecutive groups of patients. Protocol 1 was the earlier, and consisted of the combination of three agents in a sequential manner, including etoposide, thiotepa and melphalan ( n = 29), while protocol 2 employed melphalan alone ( n = 34). The two groups were comparable (other than younger age in protocol 1). Conditioning with protocol 1 seemed more toxic, as expressed by the higher number of febrile days and higher demand for parenteral nutrition. This was not expressed with longer admission time. With 108 and 60 months' median follow-up, respectively, the median survival in patients treated by protocol 2 (melphalan 200 mg/m2) was reached at 59 months, while the median survival was not yet reached in patients treated with protocol 1 ( p = 0.039). The time to progression was significantly longer with protocol 1 (median 44 months vs. 17 months with protocol 2, p = 0.033). Confounded by the small number of patients, conditioning with melphalan augmented by etoposide and thiotepa in a sequential manner is slightly more toxic than melphalan alone and may benefit patients with myeloma undergoing auto-SCT. [ABSTRACT FROM AUTHOR]

We conducted a phase I/II trial to assess the efficacy of cladribine, thiotepa and antithymocyte globulin as a reduced-intensity conditioning regimen for refractory or high-risk hematologic malignancy. The preparative regimen consisted of cladribine 5 mg/m2/day for 5 days, thiotepa 200 mg/m2/day for 3 days and ATG 3 mg/kg/day (day − 5) followed by allogeneic peripheral blood stem cell transplant. Twelve patients were transplanted from a human leukocyte antigen (HLA) matched family member. Two patients were treated at dose level I but both experienced grade IV dose limiting toxicities, and therefore the thiotepa dose was reduced to 133 mg/m2/day (dose level II). Only two of the next six patients experienced dose limiting toxicities. Median age was 46 years. At dose level II, the median time to neutrophil and platelet engraftment was 17 and 20 days, respectively. The incidence of acute and chronic graft-versus-host disease (GVHD) was 40% and 30%, respectively. Day + 100 non-relapse mortality was 0% and at 1 year was 20%. Median overall survival (OS) was 42 months and 2-year OS was 70%. Median progression-free survival (PFS) was 11 months and 2-year PFS was 40%. We conclude that the reduced-intensity conditioning regimen of cladribine, thiotepa and ATG achieved excellent donor chimerism with acceptable toxicity. [ABSTRACT FROM AUTHOR]

Treatment of primary central nervous system lymphoma (PCNSL) with high-dose methotrexate-based chemotherapy and whole-brain radiotherapy (WBRT) is associated with high rates of relapse and severe neurotoxicity. In an attempt to improve upon these poor results, we treated 21 patients with PCNSL aged 34-69 years (median 56) with high-dose thiotepa, busulfan, cyclophosphamide (TBC) and autologous stem cell transplant (ASCT) as part of front-line therapy, without WBRT. Patient characteristics included: Karnofsky performance status (KPS) <70% ( n == 17), age >60 years ( n == 8), deep brain involvement ( n == 16). Treatment-induced neurotoxicity was not observed in any of these patients. Currently, 11 of 21 patients (52%) are alive and progression-free at a median follow-up of 60 (7-125) months post-ASCT. Causes of death included progressive PCNSL ( n == 4), progressive systemic lymphoma ( n == 1), early treatment-related mortality (TRM, n == 3) and two late deaths from pneumonia 3 years post-ASCT. All patients who died of TRM were over 60 years of age and had poor performance status. In conclusion, TBC/ASCT offers potential long-term progression-free survival without neurotoxicity when used as part of upfront therapy for PCNSL. However, efforts to reduce TRM through improved patient selection and possibly through decreased intensity of the TBC regimen for older or less fit patients are recommended. [ABSTRACT FROM AUTHOR]

Unrelated cord blood transplant (CBT) is an alternative treatment option for patients who lack a matched donor. However, the optimal type and intensity of the preparative regimen remains unclear. We evaluated the toxicity and outcomes of a conditioning regimen consisting of melphalan 140 mg/m2 (day − 8), thiotepa 10 mg/kg (day − 7), fludarabine 160 mg/m2 over 4 days (days − 6 to − 3) and rabbit antithymocyte globulin (ATG) 1.25 mg/kg (day − 4) and 1.75 mg/kg (day − 3) (FMT). Forty-seven patients with advanced hematologic malignancies with a median age of 23 years (30 adults and 17 children) were treated. Sixty percent of patients were in remission at transplant. Ninety-one percent of the patients engrafted neutrophils after a median of 22 days, and all but one of the patients achieving donor engraftment had hematopoietic recovery with 100% cord blood-derived cells. Grade 3 gastrointestinal toxicity was the major non-hematopoietic toxicity, occurring in 32% of patients. Cumulative incidence of day-100 grade II-IV acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) was 53% and 34%, respectively, and non-relapse mortality at day 100 and 2 years was 11% and 40%. Two-year disease-free and overall survival rates were 31% and 44%, respectively. These results suggest that FMT is a feasible conditioning regimen for patients undergoing CBT. [ABSTRACT FROM AUTHOR]

The authors discuss the use of high-dose therapy (HDT) with thiotepa in conditioning regimens for patients with relapsed diffuse large B-cell lymphoma (DLBCL) involving the central nervous system (CNS). Topics discussed include the use of HDT therapy with autologous stem cell transplant (AuSCT) during disease progression, the utilization of intrathecal chemotherapy for CNS relapse, and the classification made by the European Medicines Agency to thiotepa as an orphan drug in 2007.

The standard approach to primary central nervous system lymphomas (PCNSL), that is high-dose methotrexate (HD-MTX)-based chemotherapy followed by whole-brain irradiation (WBRT), is associated with disappointing outcome. Moreover, this strategy is heavily conditioned by increased risk of disabling neurotoxicity, mostly among elderly patients. Several drugs and strategies have been investigated to improve results and neurotolerability. Among others, some investigators focused on the use of high-dose chemotherapy supported by autologous stem cells transplant (HDC/ASCT) as consolidation after primary chemotherapy. This approach has been used as salvage therapy in patients who experienced progressive disease or relapse after conventional chemo-radiotherapy or as consolidation after primary HD-MTX-based chemotherapy, replacing or preceding WBRT. Evidence supporting the role of HDC/ASCT is growing but several questions are still unanswered. The best conditioning regimen, the role of concomitant intrathecal chemotherapy, the neurotoxicity risk of further WBRT after transplant, the best time for response assessment and late effects both on neurological performance and extraneural organs remain to be characterised. This critical review is focused on the analysis of published experiences on HDC/ASCT in PCNSL in order to provide preliminary answers to the most pressing questions in this field. [ABSTRACT FROM AUTHOR]

Fifty-three patients with multiple myeloma (MM) underwent an allogeneic stem cell transplant (HSCT) from their HLA identical siblings using a reduced-intensity conditioning consisting of thioteopa 5 mg/kg, fludarabine 90 mg/m2, and melphalan 80 mg/m2. Their median age was 52 years (range 38 - 68) and the interval from diagnosis 12 months. Forty-three patients (82%) had advanced disease and 33 had previously been treated with high-dose therapy with one (N = 21), or more (N = 12) autologus transplants. Ten (18%) had their allograft programmed after induction chemotherapy. The majority (N = 44) received peripheral blood as stem cell source. Acute graft-versus-host disease (GVHD) grade II - IV developed in 45%, but grade III - IV in only 5%. Cumulative incidence of chronic GVHD was 64%. Sixty-two per cent were in complete remission (CR) following transplantation. Transplant-related mortality was 13%. Relapse incidence was 32%. With a median follow-up of 22 months, 3-year overall survival is 45% and progression free survival (PFS) 37%. The thiotepa, fludarabine, and melphalan conditioning regimen can produce remissions in the majority of MM patients with a limited transplant mortality rate. When used as first line treatment the results of transplantation appear even more encouraging. [ABSTRACT FROM AUTHOR]

High dose chemotherapy with autologous stem cell transplant is often used in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) who either do not respond to, or relapse after conventional chemotherapy. There is no consensus on the "ideal" pretransplant conditioning regimen. In this study, we analyzed the results of 100 consecutive patients with HD and NHL who met our eligibility criteria and underwent autologous stem cell transplant at New York Medical College and Zalmen A. Arlin Cancer Institute. All patients received high dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ). One hundred patients, 37 with HD and 63 with NHL underwent autologous stem cell transplant using TMJ as a conditioning regimen. All patients with HD had chemo-sensitive relapse while 50 patients with NHL had chemo-sensitive relapse and 13 patients had first complete remission. The source of stem cells was bone marrow (18 patients), peripheral blood (50 patients) and both bone marrow and peripheral blood (32 patients). With a median follow up of 91 months (range 23 - 147 months), the median survival of patients with HD and NHL who underwent autologous stem cell transplant is 107 months and the 5 years disease free survival is 43%. Median survival of patients with HD and NHL is 87 and 107 months respectively. There were 4 transplant related deaths. Median survival of patients who had sensitive relapse at the time of transplant is 87 months while median survival has not been reached for patients who had first complete remission at the time of transplant. Multivariate analysis identified age > 35 years ( P  = 0.02) as a predictor for poor survival for the whole group as well as for patients with NHL ( P  = 0.04). TMJ is a safe and effective regimen when used as a part of autologous stem cell transplant for patients with HD and NHL. [ABSTRACT FROM AUTHOR]

The article presents a study exploring the role of topotecan, vinorelbine, thiotepa and gemcitabine (TVTG) chemotherapy in relapsed/refractory adult acute myeloid leukemia (AML). The study suggests the very limited benefits of TVTG for AML patients due to high adverse events and therapy-related mortality rates. The authors also suggest further clinical trials to test newer agents.