Acute lymphoblastic leukemia (ALL)
Hematopoietic Stem Cell Transplantation
Hematopoietic stem cell transplantation in Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) involves mutations in genes that are essential for the normal development and proliferation of blood cells. The primary treatment objective is to eradicate leukemia cells and their precursors, aiming for remission. Following chemotherapy-induced remission, several approaches are utilized to sustain this state, including multiple rounds of consolidation chemotherapy, high-dose chemotherapy with subsequent autologous stem cell infusion to support recovery (autologous stem cell transplantation), or ongoing immunotherapy using another person's immune cells through allogeneic hematopoietic stem cell transplantation. Recently, targeted immunotherapies have been increasingly adopted to maintain remission, with numerous clinical trials in progress.
For adults with high-risk ALL, allogeneic hematopoietic stem cell transplantation is the most common strategy to maintain remission, applicable to over 85% of these patients. High-risk factors include being over 40 years old, having a high white blood cell count at diagnosis, and unfavorable chromosomal and genetic mutations. If the initial chemotherapy response is suboptimal, allogeneic stem cell transplantation is typically planned. For those not considered high-risk, effective treatment outcomes may still be achievable without allogeneic transplantation, using chemotherapy, maintenance therapy, and autologous stem cell transplantation. With improvements in detecting minimal residual disease, clinical studies are evaluating whether allogeneic transplantation can be avoided due to its significant side effects and mortality risk, especially in cases where no residual disease is found post-remission.
Concerning allogeneic stem cell transplantation, traditionally, a sibling or unrelated donor with matching HLA (major histocompatibility antigens) is sought. If a matching donor isn't available, options like umbilical cord blood or a partially matched family or unrelated donor are considered. Advancements in transplantation techniques have recently allowed for successful transplants even with complete HLA mismatches, showing results comparable to those from matched donors.
What are the outcomes of hematopoietic stem cell transplantation?
At Catholic Hematology Hospital, the success of allogeneic hematopoietic stem cell transplantation for treating acute lymphoblastic leukemia (ALL) can differ based on the patient's risk profile and the transplant type. Yet, the reported overall 5-year survival rate is about 65%. Of the patients who do not survive, roughly half succumb to relapses without reaching remission again, while the other half pass away due to infections and immune-related complications from the transplant. The hospital has shared promising results from using alternative donors, finding that survival rates with umbilical cord blood and transplants from mismatched HLA donors exceed 60% over five years, aligning closely with results from matched HLA donor transplants.
For patients with standard-risk ALL undergoing autologous stem cell transplantation, the relapse rate stands at around 25%. Despite this, the treatment-related mortality rate is below 5%, contributing to an encouraging 5-year survival rate of 71.1%.
Looking ahead, the field anticipates more tailored transplantation approaches, propelled by enhancements in detecting minimal residual disease. There's optimism that many patients may be able to avoid stem cell transplantation entirely, benefiting instead from an array of immunotargeted therapies.