Selected characteristics with therapeutic implications
| Characteristics . | Associated features . | Potential therapeutic intervention . |
|---|---|---|
| Infants with rearranged MLL | Hyperleukocytosis, CD10− B-cell precursor phenotype, increased CNS leukemia, poor prednisone response | FLT3 inhibitor (eg, lestaurtinib), tyrosine kinase inhibitor (eg, sorafenib), demethylating agents (eg, 5-azacytidine, decitabine), novel nucleoside analogs (eg, clofarabine) |
| Older adolescents | T-cell phenotype, male, increased MLL-AF4 | Intensive glucocorticoids, vincristine and asparaginase treatment, high-dose methotrexate; close monitoring of treatment adherence |
| T-cell | Hyperleukocytosis, increased CNS leukemia, male | Intensive glucocorticoids, vincristine and asparaginase treatment, high-dose methotrexate, intensive intrathecal therapy |
| Early T-cell precursor | CDla−, CD8−, CD5weak, stem cell or myeloid markers, older age, dismal prognosis | Myeloid-directed therapy (eg, high-dose cytarabine); epigenetic therapy |
| t(9;22)/BCR-ABL1 | Hyperleukocytosis, older age, precursor B-cell phenotype, poor prednisone response, IKZF1 alterations | Tyrosine kinase inhibitor (imatinib, dasatinib, nilotinib) |
| t(1;19)/TCF3-PBX1 | Pre-B phenotype, black race, increased CNS relapse | Intensive intrathecal therapy |
| t(17;19) /TCF3-HLF | Precursor B-cell phenotype, hypercalcemia, coagulopathy, dismal prognosis | Allogeneic transplant |
| Hypodiploidy < 44 chromosomes | Precursor B-cell phenotype, increased risk of relapse | Intensive treatment with very high-risk protocol |
| iAMP21 | Older age, low white blood cell count | Intensive glucocorticoids; vincristine and asparaginase treatment |
| Host TPMT activity | TPMT activity is inversely related to accumulation of active thioguanine nucleotides | Adjust thiopurine dose based on TPMT genotype or phenotype |
| High methotrexate clearance | Younger age, male | Adjust methotrexate dose based on estimated clearance |
| Presence of serum IgG antiasparaginase antibodies during therapy | Allergy to asparaginase; silent inactivation | Consider use of alternative form of asparaginase |
| Characteristics . | Associated features . | Potential therapeutic intervention . |
|---|---|---|
| Infants with rearranged MLL | Hyperleukocytosis, CD10− B-cell precursor phenotype, increased CNS leukemia, poor prednisone response | FLT3 inhibitor (eg, lestaurtinib), tyrosine kinase inhibitor (eg, sorafenib), demethylating agents (eg, 5-azacytidine, decitabine), novel nucleoside analogs (eg, clofarabine) |
| Older adolescents | T-cell phenotype, male, increased MLL-AF4 | Intensive glucocorticoids, vincristine and asparaginase treatment, high-dose methotrexate; close monitoring of treatment adherence |
| T-cell | Hyperleukocytosis, increased CNS leukemia, male | Intensive glucocorticoids, vincristine and asparaginase treatment, high-dose methotrexate, intensive intrathecal therapy |
| Early T-cell precursor | CDla−, CD8−, CD5weak, stem cell or myeloid markers, older age, dismal prognosis | Myeloid-directed therapy (eg, high-dose cytarabine); epigenetic therapy |
| t(9;22)/BCR-ABL1 | Hyperleukocytosis, older age, precursor B-cell phenotype, poor prednisone response, IKZF1 alterations | Tyrosine kinase inhibitor (imatinib, dasatinib, nilotinib) |
| t(1;19)/TCF3-PBX1 | Pre-B phenotype, black race, increased CNS relapse | Intensive intrathecal therapy |
| t(17;19) /TCF3-HLF | Precursor B-cell phenotype, hypercalcemia, coagulopathy, dismal prognosis | Allogeneic transplant |
| Hypodiploidy < 44 chromosomes | Precursor B-cell phenotype, increased risk of relapse | Intensive treatment with very high-risk protocol |
| iAMP21 | Older age, low white blood cell count | Intensive glucocorticoids; vincristine and asparaginase treatment |
| Host TPMT activity | TPMT activity is inversely related to accumulation of active thioguanine nucleotides | Adjust thiopurine dose based on TPMT genotype or phenotype |
| High methotrexate clearance | Younger age, male | Adjust methotrexate dose based on estimated clearance |
| Presence of serum IgG antiasparaginase antibodies during therapy | Allergy to asparaginase; silent inactivation | Consider use of alternative form of asparaginase |
iAMP21 indicates intrachromosomal amplification of chromosome 21; and TPMT, thiopurine methyltransferase.