Dasatinib followed by second allogeneic hematopoietic stem cell transplantation for relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia after the first transplantation

Abstract

Although allogeneic hematopoietic stem cell transplantation (HSCT) is an established treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL), the prognosis of patients who relapse after allogeneic HSCT has been extremely poor. Dasatinib, a second-generation tyrosine kinase inhibitor, is a promising agent for the treatment of Ph-ALL. We report on a Ph-ALL patient who relapsed early after the first allogeneic HSCT, but achieved complete molecular remission with dasatinib alone. She remains in molecular remission 12 months after the second allogeneic HSCT. Dasatinib was generally well tolerated, but she developed myalgia, nausea and positive cytomegalovirus antigenemia. In addition, sudden-onset bloody diarrhea was observed 10 days after the second HSCT, which was possibly associated with the use of dasatinib in addition to the effect of the conditioning regimen and graft-versus-host disease. In conclusion, dasatinib is an effective agent for Ph-ALL with a poor prognosis, but may be associated with specific adverse events including opportunistic infection and gastrointestinal bleeding.

Current Treatment of Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia

“…Under these circumstances, a second allo-HSCT might be considered. A case report 37 shows a positive outcome for a patient who received dasatinib followed by a RIC alloHSCT after imatinib and myeloablative alloHSCT failed to control the disease. All reports of alloHSCT show a very much less than ideal outcome in patients beyond CR1.…”

Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia

“…1,2 Based on improvements in efficacy and tolerability, next-generation TKIs have been widely used in first-line treatments for chronic myeloid leukemia (CML), 3,4 and dasatinib is used in second-line treatments for patients with Ph-pos ALL that failed to respond or were intolerant to imatinib 5 or another first-line agent. 6 Nilotinib is a TKI with a potent binding affinity for BCR-ABL1 tyrosine kinase.…”

NCCN Guidelines Insights: Acute Lymphoblastic Leukemia, Version 1.2017

“…Some investigators have reported on the feasibility of inducing a second molecular CR with dasatinib in those who have experienced an early relapse NCCN Guidelines Insights CE after first allogeneic HCT, which allowed for a second allogeneic HCT. 48,49 Studies that include donor lymphocyte infusion (DLI) to induce further graftversus-leukemia effect in patients who experience relapse after allogeneic HCT have reported little to no benefit, although it has been suggested that this is due to an excessively high leukemic burden. 50,51 Published case reports have suggested that the use of DLI for residual disease or molecular relapse (as noted by levels of BCR-ABL fusion mRNA measured with PCR) after allogeneic HCT may eliminate residual leukemic clones and thereby prevent overt hematologic relapse.…”