Acute Lymphoblastic Leukemia (ALL)

The diagnosis and treatment of lymphoid neoplasms have undergone a continuously progressive positive change in the last three decades, with accelerated progress in the previous decade due to the advent of genomics in cancer diagnosis. Significantly, there has been an increasing emphasis on integrating molecular genetics with clinical, morphological, immunophenotypic, and cytogenetic evaluation for diagnosis. As we think of moving forward with further advances in the genomics era, it will be first helpful to understand our current state of knowledge and how we achieved it in the challenging and complex field of lymphoid neoplasms, which comprise very heterogeneous neoplastic diseases in children and adults, including clinically acute lymphoblastic leukemias (ALLs) arising from precursor lymphoid cells and clinically indolent and aggressive lymphomas arising from mature lymphoid cells. This work aims to provide an overview of the historical evolution and the current state of knowledge to anyone interested in the field of lymphoid neoplasms, including students, physicians, and researchers. Therefore, I have discussed this complex topic in three review manuscripts, designated Parts 1–3. In Part 1, I explain the basis of the diagnostic classification of lymphoid neoplasms and its evolution up to the current fifth edition of the World Health Organization classification of hematolymphoid neoplasms and the crucial importance of diagnostic tumor classifications in achieving and advancing patient care and precision medicine. In the second and third manuscripts, I discuss current diagnostic considerations for B-ALL and T-ALL (Part 2) and common indolent and aggressive mature leukemias/lymphomas (Part 3), including significant updates in the WHO 2022 classification, newly described entities, and concepts, including genetic predisposition to ALLs and lymphomas, and emphasizing throughout the essential integration of molecular genetics with clinical, morphologic, immunophenotypic, and cytogenetic evaluation, as required for the precise diagnosis of the type of lymphoma/leukemia in any patient. Full article

Cure rates now exceed 90% in many contemporary trials for children with B-cell acute lymphoblastic leukemia (B-ALL). However, treatment remains suboptimal, and therapy is toxic for all patients. New treatment options potentially offer the chance to reduce both treatment resistance and toxicity. Here, we review recent advances in ALL diagnostics, chemotherapy, and immunotherapy. In addition to describing recently published results, we also attempt to project the impact of these new developments into the future to imagine what B-ALL therapy may look like in the next few years. Full article