The past 2 decades have been a remarkable period of progress not only in the diagnostics, but also in the therapeutics of cancer in general and hematologic malignancies (HMs) in particular. Modern technology; namely molecular genetics, DNA sequencing and genomic as well as epigenetic assays; is the main driving force behind the recent advances in the medical diagnostics and therapeutics and the subsequent transformation of some HMs into the era of precision medicine. Hematopoietic stem cell transplantation (HSCT) provides a life-prolonging or potentially curative therapeutic option for patients with HMs. Although allogeneic HSCT with myeloablative conditioning therapy is still the only potentially curative therapy for some HMs, it is associated with relatively high treatment-related mortality due to the graft versus host disease and infectious complications. Non-myeloablative and reduced-intensity forms of allogeneic HSCT provide safer alternative forms of transplantation for older patients and those with comorbid medical conditions. The recent advances in haploidentical HSCT have made this form of allografting a valid and a safe form of transplant for patients with HMs lacking human leukocyte antigen (HLA)-identical donors with outcomes equivalent to allografts obtained from HLA-matching sibling donors. In patients with HMs, the indications for allogeneic HSCT are changing with time and this is reflected by the widespread utilization of novel and targeted therapies recently. Allogeneic HSCT was the most frequent indication for patients with chronic myeloid leukemia (CML) in the 1980s and 1990s. Currently, the vast majority of patients with CML are treated with various tyrosine kinase inhibitors (TKIs) and allogeneic HSCT is reserved for certain indications. Acute promyelocytic leukemia is currently treated with novel therapies and HSCT is also reserved for specific indications. In recent years, allogeneic HSCT is mainly performed for patients with myelodysplastic syndrome and acute myeloid leukemia while autologous HSCT is still indicated for patients with multiple myeloma, Hodgkin's lymphoma and non-Hodgkin's lymphoma. Currently, novel and targeted therapies are used: (1) prior to HSCT to reduce tumor burden and to bridge to transplantation, (2) as part of conditioning therapy in place of or in conjunction with conventional chemotherapeutic agents, or (3) following HSCT as maintenance therapy to allow long-term disease control or as salvage therapy in case of relapse of HMs after HSCT. Examples of the novel and targeted therapies that are currently used in HMs are: TKIs, Janus kinase inhibitors, immunomodulatory agents, proteasome inhibitors, FMS-like tyrosine kinase-3 inhibitors, Bruton's TKIs, chimeric antigen receptor (CAR)-T cells, checkpoint inhibitors and monoclonal antibodies. However, novel and targeted therapies have their own adverse effects and their long-term use has been associated with drug resistance and clonal evolution. Novel and targeted therapies should not be considered as a form of replacement to HSCT, but instead these 2 valuable therapeutic options should be considered as complimentary to each other. The smart combination of novel agents and targeted therapies with various forms of HSCT in the new treatment paradigm of HMs will ultimately lead to higher cure rates and longer disease control. Contributions to this topic are expected to highlight the importance of both HSCT and novel therapies in the treatment of patients with HMs by including balanced reviews of recent literature.
|Dr. Khalid Ahmed Al-Anazi
King Fahad Specialist Hospital (KFSH)
Submission date: 2018-01-30