Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI]-Treatment of Relapsed Childhood ALL

Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment of Relapsed Childhood ALL

Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] Guide

• General Information About Childhood Acute Lymphoblastic Leukemia (ALL)
• Risk-based Treatment Assignment
• Treatment Option Overview for Childhood ALL
• Treatment for Newly Diagnosed Childhood ALL
• Postinduction Treatment for Childhood ALL
• CNS-directed Therapy for Childhood ALL
• Postinduction Treatment for Specific ALL Subgroups
• Treatment of Relapsed Childhood ALL
• Changes to this Summary (05 / 02 / 2014)
• About This PDQ Summary
• Get More Information From NCI

T-cell ALL

For patients with T-cell ALL who achieved remission after bone marrow relapse, outcomes with postreinduction chemotherapy alone have generally been poor,[5] and these patients are usually treated with allogeneic HSCT in CR2, regardless of time to relapse.

Standard Treatment for Second and Subsequent Bone Marrow Relapse

Although there are no studies directly comparing chemotherapy with HSCT for patients in third or subsequent CR, because cure with chemotherapy alone is rare, transplant is generally considered a reasonable approach for those achieving remission. Long-term survival for all patients after a second relapse is particularly poor, in the range of less than 10% to 20%.[45] One of the main reasons for this is failure to obtain a third remission. In spite of numerous attempts at novel combination approaches, only about 40% of children with second relapse are able to achieve remission.[52] If these patients achieve CR, HSCT has been shown to cure 20% to 35%, with failures occurring due to high rates of relapse and transplant-related mortality.[53,54,55,56,57][Level of evidence: 3iiA]

Hematopoietic Stem Cell Transplantation for First and Subsequent Bone Marrow Relapse

Components of the transplantation process

An updated expert panel review of indications for HSCT has been published.[58] Components of the transplant process that have been shown to be important in improving or predicting outcome of HSCT for children with ALL include the following:

1. Total-body irradiation (TBI)-containing transplant preparative regimens.
2. MRD detection just before transplant.
3. Donor type and HLA match.
4. Immune modulation after transplant to prevent relapse.

TBI-containing transplant preparative regimens

For patients proceeding to allogeneic HSCT, TBI appears to be an important component of the conditioning regimen. Two retrospective studies and a randomized trial suggest that transplant conditioning regimens that include TBI produce higher cure rates than do chemotherapy-only preparative regimens.[39,59,60] Fractionated TBI (total dose, 12-14 Gy) is often combined with cyclophosphamide, etoposide, thiotepa, or a combination of these agents. Study findings with these combinations have generally resulted in similar rates of survival,[61,62,63] although one study suggested that if cyclophosphamide is used without other chemotherapy drugs, a dose of TBI in the higher range may be necessary.[64] Many standard regimens include cyclophosphamide with TBI dosing between 1.32 and 1.4 Gy. On the other hand, when cyclophosphamide and etoposide were used with TBI, doses above 1.2 Gy resulted in worse survival due to excessive toxicity.[62]