Abstract
We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment. The bone marrow evaluation after 2, 3, 6, 10 and 13 months was negative for MRD. After starting ponatinib, the patient experienced a skin graft-versus-host disease (GVHD), whereas no occurrence of GVHD was observed after transplant, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect, but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib was well tolerated but a thyroid dysfunction mimicking a cardiovascular toxicity was observed and solved with hormonal substitutive treatment.
| Original language | English |
|---|---|
| Pages (from-to) | 58-61 |
| Number of pages | 4 |
| Journal | Chemotherapy |
| DOIs | |
| Publication status | Accepted/In press - Sep 10 2016 |
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Keywords
- Acute lymphoblastic leukemia
- Allogeneic transplant
- Graft-versus-host disease
- Graft-versus-leukemia effect
- Philadelphia chromosome
- Ponatinib
- T315I mutation
- Thyroid dysfunction
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Drug Discovery
- Pharmacology (medical)
- Infectious Diseases
Cite this
Ponatinib Induces a Persistent Molecular Response and Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia with a T315I Mutation following Early Relapse after Allogeneic Transplant. / Renzi, Daniela; Marchesi, Francesco; De Angelis, Gottardo; Elia, Loredana; Salvatorelli, Emanuela; Gumenyuk, Svitlana; Palombi, Francesca; Pisani, Francesco; Romano, Atelda; Spadea, Antonio; Papa, Elena; Canfora, Marco; Arcese, William; Mengarelli, Andrea.
In: Chemotherapy, 10.09.2016, p. 58-61.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ponatinib Induces a Persistent Molecular Response and Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia with a T315I Mutation following Early Relapse after Allogeneic Transplant
AU - Renzi, Daniela
AU - Marchesi, Francesco
AU - De Angelis, Gottardo
AU - Elia, Loredana
AU - Salvatorelli, Emanuela
AU - Gumenyuk, Svitlana
AU - Palombi, Francesca
AU - Pisani, Francesco
AU - Romano, Atelda
AU - Spadea, Antonio
AU - Papa, Elena
AU - Canfora, Marco
AU - Arcese, William
AU - Mengarelli, Andrea
N1 - Bisogna inserire Marchesi F.
PY - 2016/9/10
Y1 - 2016/9/10
N2 - We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment. The bone marrow evaluation after 2, 3, 6, 10 and 13 months was negative for MRD. After starting ponatinib, the patient experienced a skin graft-versus-host disease (GVHD), whereas no occurrence of GVHD was observed after transplant, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect, but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib was well tolerated but a thyroid dysfunction mimicking a cardiovascular toxicity was observed and solved with hormonal substitutive treatment.
AB - We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment. The bone marrow evaluation after 2, 3, 6, 10 and 13 months was negative for MRD. After starting ponatinib, the patient experienced a skin graft-versus-host disease (GVHD), whereas no occurrence of GVHD was observed after transplant, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect, but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib was well tolerated but a thyroid dysfunction mimicking a cardiovascular toxicity was observed and solved with hormonal substitutive treatment.
KW - Acute lymphoblastic leukemia
KW - Allogeneic transplant
KW - Graft-versus-host disease
KW - Graft-versus-leukemia effect
KW - Philadelphia chromosome
KW - Ponatinib
KW - T315I mutation
KW - Thyroid dysfunction
UR - http://www.scopus.com/inward/record.url?scp=84988419025&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84988419025&partnerID=8YFLogxK
U2 - 10.1159/000448750
DO - 10.1159/000448750
M3 - Article
AN - SCOPUS:84988419025
SP - 58
EP - 61
JO - Chemotherapy
JF - Chemotherapy
SN - 0009-3157
ER -