Comparison of Preparative Regimens in Transplants for Children With Acute Lymphoblastic Leukemia

TBI has been used widely in the setting of BMT over the past 3 decades. Early research demonstrated feasibility and efficacy in the myeloablative setting, in preparation first for allogenic BMT and later for autologous stem cell rescue. As experience with TBI increased, its dual roles of myeloablation and immunosuppression came to be recognized. Toxicity associated with myeloablative TBI remains significant, and this treatment is generally reserved for younger patients with excellent performance status. Reduced intensity conditioning regimens may be useful to provide immunosuppression for patients who are not candidates for myeloablative treatment. Efforts to reduce toxicity through protection of normal tissue using methods of normal tissue blocking and use of TLI, rather than TBI, continue. In the future, modalities such as helical tomotherapy, proton radiotherapy and radioimmunotherapy, may have roles in delivery of radiation to the BM and lymphoid structures with reduced normal tissue toxicity. With further investigation, these efforts may expand the therapeutic ratio associated with TBI, allowing safer delivery to a broader range of patients.

Section: Introduction and Historical Perspectivementioning

confidence: 99%

TBI during BM and SCT: review of the past, discussion of the present and consideration of future directions

Hill‐Kayser

Plastaras

Tochner

et al. 2010

“…13 The clinical efficacy of chemotherapy-only regimens over fTBI-containing regimens in the conditioning of patients with ALL and over the age of 2 years has not been established. 7 For patients above the age of 2-3 years but not eligible for fTBI (for example, those with a history of high-dose irradiation), chemotherapy-only regimens (for example, BU/CY/melphalan (Mel)) are employed. 12 fTBI-based regimens have been employed also among patients under the age of 18 months, particularly in the unrelated setting.…”

Section: Acute Lymphoblastic Leukemiamentioning

confidence: 99%

“…TBI, fractionated (fTBI) in most cases and combined with CY, has been extensively employed due to its substantial immunosuppressive potential, lack of cross-reactivity with other modalities and sanctuary sparing as well as effective antileukemic potential as the backbone of the conditioning regimen in transplants performed for pediatric ALL [1][2][3][4][5][6][7] in the matched related, matched unrelated and mismatched settings. Cumulative doses up to 10-14 Gy have been used with many groups reducing the pulmonary cumulative dose down to [8][9] Gy and the use of fTBI to patients above the age of 2 years.…”

Section: Acute Lymphoblastic Leukemiamentioning

confidence: 99%

Current European practice in pediatric myeloablative conditioning

Vettenranta

2008

Myeloablative conditioning continues to be employed in hematopoietic stem cell transplantation among patients with pediatric transplant indications. Fractionated TBI (fTBI) remains, with its considerable anti-leukemic potential, the cornerstone of conditioning in the most common of pediatric indications, ALL in its first, second or subsequent remission despite its well-established longterm sequelae. The feasibility of chemotherapy-only regimens has been established and these regimens widely employed in other pediatric indications, for example, in ALL below the age of 2 years, AML, myelodysplasias or severe aplastic anemia. Conditioning regimens are being modified with data accumulating on the role of, for example, pre-transplant residual disease, advanced HLAtyping or haploidentical transplantations in the pediatric setting.

“…However, in retrospective studies from International Bone Marrow Transplant Registry and Germany, the TBI-cyclophosphamide regimen was superior to the non-TBI-containing busulfan-based regimen. 10,13 Hence, these data demonstrate a strong need to evaluate new drugs with a lower toxicity as conditioning regimen for patients with acute lymphoblastic leukemia. Treosulfan as part of the conditioning regimen might be an alternative to TBI-based regimens.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic stem cell transplantation after conditioning with treosulfan, etoposide and cyclophosphamide for patients with ALL: a phase II-study on behalf of the German Cooperative Transplant Study Group and ALL Study Group (GMALL)

Bornhäuser

Stelljes

Pichlmeier

et al. 2015

TBI-based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with ALL. We investigated toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide and cyclophosphamide for ALL within a prospective study. Major inclusion criteria were CR and non-eligibility for TBI. Fifty patients with a median age of 46.5 years (range, 18-64) were included. Donors were HLA-identical sibling (n = 8), matched (n = 42) or mismatched (n = 10) unrelated. The toxicity was moderate, resulting in a cumulative incidence of non-relapse mortality (NRM) at 1 year of 8% (90% confidence interval: 2-15%). Acute GvHD grade II-IV and grade III/IV was noted in 53% and 14%, respectively. Chronic GvHD at one year was seen in 41%. After a median follow-up of 24 months the cumulative incidence of relapse was 36% (90% confidence interval: 24-48) and 51% (90% confidence interval: 37-65) at 1 and 2 years, respectively. The estimated 2-year disease-free and overall survivals were 36 and 48%, respectively. Treosulfan, etoposide and cyclophosphamide followed by AHSC has a favorable toxicity profile with low NRM and therefore represents a potential alternative regimen for ALL in 1. CR (NCT00682305).