AL-03. Successful allogeneic stem cell transplantation in a female patient with therapy-related acute promyelocytic leukemia
Mikhail M. Kanunnikov, Alexandra V. Lapina, Zarema K. Abdulkhalikova, Bella I. Ayubova, Julija J. Vlasova, Marina O. Popova, Alexander D. Kulagin, Sergey N. Bondarenko
RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, St. Petersburg, Russia
Contact: Dr. Sergey N. Bondarenko, e-mail: email@example.com
Previous polychemotherapy (PCT) with the use of topoisomerase II inhibitors applied in the treatment of malignant neoplasms is a risk factor for the development of secondary acute promyelocytic leukemia (APL associated with therapy, t-APL). Usually, t-APL develops 3 years after previous chemotherapy and has a poor response to conventional PCT. We present a case report of successful treatment of t-APL that has developed after combined treatment of breast cancer by allogenic hematopoietic stem cell transplant (HSCT).
A 45-year-old female patient undergone radical mastectomy in 2013 for combined (invasive lobular and ductal) breast cancer (stage IIA, pT1cN1M0) followed by six courses of chemotherapy with doxorubicin, irradiation and hormonal therapy with tamoxifen were carried out. Three years later, acute promyelocytic leukemia (APL) was diagnosed. The course of disease was a resistant and recurrent, conventional polychemotherapy was performed according to the AIDA protocol, relapse therapy using all-trans-retinoic acid (ATRA), arsenic trioxide (ATO) and gemtuzumab-ozogamicin (GO). The post-treatment period was complicated by febrile neutropenia, sepsis, ATO cardiotoxicity, differentiation syndrome. In 2019, as part of the consolidation in the 3rd clinical and hematological remission (molecular remission was not achieved), allo-HSCT was performed. The unrelated male donor from the Russian donor registry was partially compatible (9/10 HLA antigens). A reduced-toxicity conditioning regimen included: fludarabine 30 mg/m2, melphalan 100 mg/m2. GvHD prevention was as follows: cyclophosphamide 50 mg/kg day+3, day+4, tacrolimus 0.02 mg/kg, mycophenolate mofetil (MMF) 45mg/kg. Peripheral blood stem cells were used as a transplant source.
Graft engraftment was achieved on day +22 from HSCT. The complete remission of APL was achieved with full donor chimerism. 1 month later, the patient suffered COVID-19 pneumonia and reactivation of cytomegalovirus infection. The patient received antimicrobial therapy (meropenem, ganciclovir), as well as plasma transfusions of COVID-19 reconvalescents. After 1 month, PCR results for COVID-19 and CMV were negative. According to the chest CT data, there is a clear positive dynamics in the form of regression of previous changes in the lung tissue. Currently, the patient continues to be monitored at our center, remission of the underlying disease remains, and there is no chronic GvHD. The patient’s quality of life is good.
This report confirms that prior therapy (chemo-, radio- and hormonotherapy) of solid malignancies could be a risk factor of development t-APL. The patients with t-APL are at an increased risk of developing cardiotoxicity because of previous anthracycline exposure. HSCT has generally been recommended because these cases poorly respond to conventional chemotherapy.
Acute promyelocytic leukemia, secondary, allogeneic hematopoietic stem cell transplantation.