Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Adults

Abstract

Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) is the most common subtype of B-ALL in adults and its incidence increases with age. It is characterized by the presence of BCR-ABL oncoprotein that plays a central role in the leukemogenesis of Ph+ ALL. Ph+ ALL patients traditionally had dismal prognosis and long-term survivors were only observed among patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1). However, feasibility of allo-HSCT is limited in this elderly population. Fortunately, development of increasingly powerful tyrosine kinase inhibitors (TKIs) from the beginning of the 2000′s dramatically improved the prognosis of Ph+ ALL patients with complete response rates above 90%, deep molecular responses and prolonged survival, altogether with good tolerance. TKIs became the keystone of Ph+ ALL management and their great efficacy led to develop reduced-intensity chemotherapy backbones. Subsequent introduction of blinatumomab allowed going further with development of chemo free strategies. This review will focus on these amazing recent advances as well as novel therapeutic strategies in adult Ph+ ALL.

Treatment of patients with acute lymphoblastic leukemia who are not suitable for high-dose chemotherapy and hematopoietic stem cell transplantation

“…Generally, unfit patients demand less intensive therapy, based on corticosteroids, vincristine and asparaginase, avoiding anthracyclines and alkylat-ing agents, because of treatment-related mortality. In 2021., the National Comprehensive Cancer Network (NCCN) issued guidelines for the treatment of the ALL Ph+ unfit patients [8,9], which is shown in Scheme 1.…”

Dasatinib-induced spleen contraction leads to transient lymphocytosis

“…Dasatinib is also being used as maintenance after hematopoietic stem cell transplantation for high-risk Ph + ALL patients (5). Moreover, the future immunotherapeutic strategy of Ph+ ALL foresees the use of dasatinib in combination with monoclonal antibodies such as blinatumomab (6,7). Among many off-targets beyond the BCR-ABL core network, dasatinib inhibits the activity of the platelet-derived growth factor receptor (PDGFR), EphA2, c-KIT, and kinases involved in cytoskeleton and chromatin-remodeling and in lymphocyte activation (8).…”

BCR-ABL1-positive and BCR-ABL1-negative acute lymphoblastic leukaemia: description of three clinical cases and literature review

“…Своевременная и точная диагностика помогает оценить риск прогрессирования лейкоза и разработать персонализированное лечение. В эру до ингибиторов тирозинкиназы (ИТК) достижение полной ремиссии встречалось реже, чем в случаях с BCR-ABL1-негативным (BCR-ABL1-) ОЛЛ, будучи ниже 70% у всех пациентов, с показателем общей выживаемости менее 20% и различными исходами в зависимости от постиндукционного лечения [7]. В тоже время подростки и молодые люди с BCR-ABL1-ОЛЛ представляют собой уникальную популяцию пациентов с непропорционально низкой выживаемостью по сравнению с детьми младшего возраста [9].…”

“…Ph-подобный ОЛЛ обычно связан с более агрессивной эволюцией, отрицательными ответами и более низкими показателями выживаемости [10]. Пациенты с BCR-ABL1+ ОЛЛ традиционно имели неблагоприятный прогноз, и длительная выживаемость отмечалась среди пациентов, перенесших аллогенную трансплантацию стволовых гемопоэтических клеток (алло-ТСГК) впервой полной ремиссии [7]. Однако осуществимость алло-ТСГК у пожилой категории пациентов ограничена.…”