hd-idarubicin/etoposide intensified conditioning regimen allo-hsct for adult all

Conditions: Acute Lymphoblastic Leukemia

Summary: intensified conditioning regimen allo-hsct is based on a hypothesis of that intensifying condition with less-used drugs could overcome resistance,reduce tumor burden, and most importantly, spare enough time for slow-growing gvl effect following immune reconstitution to finally get rid of mrd and control the disease. our previous trial of hde-all-2011 (nct01457040) have confirmed the role of intensified conditioning allo-hsct in adult all, resulting in significantly improved os and efs in comparison with previous standard tbi/cy2 conditioning regimen(data not yet published). but at the same time, fa-tbi/cy2-vp16 conditioning regimen was associated with high transplantation-related mortality (trm), which might be attributed to excessive suppression on both bone marrow and immune. tt-all-hie-2013, substituting fa with idarubicin, is aimed at maintaining anti-tumor effect with less cross-resistance and immune suppression and reducing trm.

it's well-known that the long-term outcome of adult acute lymphoblastic leukemia (all) lags far behind that of pediatric all,associated with different molecular cytogenetics make-up and treatment strategies. in search of an optimal regimen for pediatric all, comprehensive series of clinical trials of intensive chemotherapies have been conducted and lead to 80%-90% long-term survival. at the same time, pediatric-inspired chemotherapy protocol aslo yielded a charming result of 50-60% 3-year efs in adolescent and young adult. in comparison with the leading role of intensive chemotherapy in pediatric all, allogeneic hematopoietic stem cell transplantation (allo-hsct) plays an important role in treatment strategy of adult all. according to the state-of-art understanding of all, total therapy of all should consist of molecular-cytogenetics classification at diagnosis, minimal residual disease (mrd) monitoring and redefining risk classification during treatment, pediatric-inspired chemotherapy with high-dose methotrexate/l-asparaginase during consolidation therapy,furthermore,risk/mrd-adapted allo-hsct for high-risk and refractory/relapsed all.in pre-pediatric-inspired protocol era, allo-hsct still represents the major role for improving the outcome of adult all, especially for high-risk and refractory/relapsed all. it's established that graft-versus-leukemia (gvl) effect was weak in all and patient shows poor response for donor-lymphocyte infusion (dli). intensified conditioning regimen allo-hsct is based on a hypothesis of that intensifying condition with less-used drugs could overcome resistance,reduce tumor burden, and most importantly, spare enough time for slow-growing gvl effect following immune reconstitution to finally get rid of mrd and control the disease. our previous trial of hde-all-2011 (nct01457040) have confirmed the role of intensified conditioning allo-hsct in adult all, resulting in significantly improved os and efs in comparison with previous standard tbi/cy2 conditioning regimen(data not yet published). but at the same time, fa-tbi/cy2-vp16 conditioning regimen was associated with high transplantation-related mortality (trm), which might be attributed to excessive suppression on both bone marrow and immune. tt-all-hie-2013, substituting fa with idarubicin, is aimed at maintaining anti-tumor effect with less cross-resistance and immune suppression and reducing trm.

Eligibility criteria:
inclusion criteria: 1. age: 16 years to 65 years; 2. diagnosis of acute lymphoblastic leukemia; 3. patient receives allo-hsct; 4. the informed consent form has been signed; exclusion criteria: 1. patient with severe cardiac dysfunction with less than 50% ef; 2. patient with severe lung dysfunction; 3. patient with more than 3 times uln of serum alt or ast levels, or with more than 2 times uln of serum tbil level, or less than 40% of normal prothrombin time activity (pta); or with more than 2 times the uln of serum cr; 4. patient with severe active infection; 5. patient with allergy history about suspected drug in conditioning regimen; 6. patient with other conditions considered unsuitable for the study.

Keywords: idarubicin etoposide hsct acute lymphoblastic leukemia