Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Postinduction Treatment for Specific ALL Subgroups
For infants with MLL gene rearrangement, the EFS rates continue to be in the 17% to 40% range.[12,13,15,16,17][Level of evidence: 2A] Factors predicting poor outcome for infants with MLL translocations include the following:; [Level of evidence: 3iDii]
- A very young age (<6 months).
- Extremely high presenting leukocyte count (≥200,000–300,000/μL).
- High levels of MRD at the end of induction and consolidation phases of treatment.
Treatment options for infants withMLLtranslocations
Infants with MLL gene translocations are generally treated on intensified chemotherapy regimens using agents not typically incorporated into frontline therapy for older children with ALL. However, despite these intensified approaches, EFS rates remain poor for these patients.
Evidence (intensified chemotherapy regimens for infants with MLL translocations):
- The international Interfant clinical trials consortium utilized a cytarabine-intensive chemotherapy regimen, with increased exposure to both low- and high-dose cytarabine during the first few months of therapy, resulting in a 5-year EFS of 37% for infants with MLL translocations.
- The COG tested intensification of therapy with a regimen including multiple doses of high-dose methotrexate, cyclophosphamide, and etoposide, resulting in a 5-year EFS of 34%.
The role of allogeneic stem cell transplant (SCT) during first remission in infants with MLL gene translocations remains controversial. Case series have suggested that allogeneic transplants in first remission may be effective.[19,20,21]; [Level of evidence: 3iA]
Evidence (allogeneic SCT in first remission for infants with MLL translocations):
- On a Japanese clinical trial conducted between 1998 and 2002, all infants with MLL-rearrangement were intended to proceed to allogeneic SCT from the best available donor (related, unrelated, or umbilical cord) 3 to 5 months after diagnosis.
- The 3-year EFS for all enrolled infants was 44%. This result was due, in part, to the high frequency of early relapses, even with intensive chemotherapy; of the 41 infants with MLL-rearrangement on that study who achieved complete remission (CR), 11 infants (27%) relapsed prior to proceeding to transplant.
- In a COG report that included 189 infants treated on CCG or POG infant ALL protocols between 1996 and 2000, there was no difference in EFS between patients who underwent SCT in first CR and those who received chemotherapy alone.
- The Interfant clinical trials group, after adjusting for waiting time to transplantation, also did not observe any difference in disease-free survival (DFS) in high-risk infants (defined by prednisone response) with MLL translocations treated on the Interfant-99 trial with either allogeneic SCT in first CR or chemotherapy alone.
- In a subset analysis from the same trial, allogeneic SCT in first remission was associated with a significantly better DFS for infants with MLL translocations who were younger than 6 months at diagnosis and had either a poor response to steroids at day 8 or leukocyte levels of at least 300 g/L. In this subset, SCT in first remission was associated with a 64% reduction in the risk of failure resulting from relapse or death compared with chemotherapy alone.