According to results recently presented at the 43rd annual meeting of the American Society of Hematology, children with Philadelphia-positive ALL appear to have superior survival rates when their first remission is followed with allogeneic bone marrow transplantation rather than chemotherapy.
ALL, also called acute lymphoblastic leukemia, is a cancer of the bone marrow and lymph system. The bone marrow produces early blood-forming cells, called stem cells, which grow and mature into the three blood cell types: white blood cells, which fight infection; red blood cells, which carry oxygen to tissue; and platelets, which help blood to clot. ALL is characterized by uncontrolled production of immature lymphocytes (white blood cells), of which there are two types: B and T cells. These immature lymphocytes never mature enough to perform their specific function of fighting infection. In addition, these rapidly dividing cells crowd out and suppress the formation of other important blood cells, such as red blood cells, platelets and other white blood cells. ALL is an aggressive cancer that must be treated aggressively for optimal chances of a cure.
In some cases of ALL, there is a specific genetic abnormality referred to as the Philadelphia positive (Ph+) chromosome. The Ph+ chromosome occurs through a switching of specific genetic information. The result of this genetic switching produces a protein called the Bcr-Abl tyrosine kinase. The Bcr-Abl tyrosine kinase protein facilitates cellular function and growth by modulating certain chemical information flow into and out of cells, and initiating growth responses to chemical stimuli. The pivotal problem with Bcr-Abl tyrosine kinase is that it performs its functions in an uncontrolled manner, leading to excessive replication and growth of cells. Ph+ ALL does not respond well to current treatment regimens and these patients have poor prognosis for survival.
Standard treatment for children with ALL consists of remission induction, which is initial therapy utilized to induce a remission (disappearance of cancer) followed by consolidation therapy, which is therapy used during a complete remission to kill any cancer cells that may have remained following previous therapy. Remission induction therapies often use BFM, an intensive combination chemotherapy regimen, which is usually followed by consolidation therapy consisting of additional chemotherapy.
However, because Ph+ ALL does not respond well to standard therapies, some researchers are exploring the results of using high-dose chemotherapy followed by bone marrow transplantation instead of chemotherapy alone following remission induction. High-dose chemotherapy and/or radiation tend to be more effective at killing cancer cells than lower doses of therapy. However, the high doses also kill blood-forming cells (stem cells) that are produced in the bone marrow, leaving patients susceptible to infection, anemia and uncontrolled bleeding. In order to rescue low levels of blood cells caused by high-dose therapy, stem cells are collected from bone marrow, stored and then infused into the patient following the high-dose therapy. In an allogeneic bone marrow transplant (BMT), stem cells are collected from a related or unrelated donor. Because BMT may cause severe side effects or mortality, there is reluctance among patients and physicians to use BMT unless scientific evidence suggests it is highly effective.
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Canadian researchers recently conducted a clinical trial to compare the survival rates of 21 children with Ph+ ALL in first remission who received allogeneic BMT or chemotherapy alone as consolidation therapy. Ten children underwent allogeneic BMT and 11 received chemotherapy. All children had previously received a BFM-based remission induction therapy. After four years, 58% of the children who received allogeneic BMT were free of cancer or cancer-related complications. This is significantly higher than the children who received chemotherapy (33%). However, the transplant-related mortality for children receiving BMT was 20%.
The researchers conducting this clinical trial concluded that allogeneic BMT during the first remission of Ph+ ALL children appears to significantly improve survival rates and should replace chemotherapy as standard consolidation therapy. The researchers also acknowledge that the issue of unrelated donor transplantation requires further exploration. Individuals with Ph+ ALL may wish to speak with their physician regarding the risks and benefits of allogeneic BMT or about participating in a clinical trial evaluating Gleevec® or other novel therapeutic approaches. Two sources of information regarding ongoing information on clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (
www.eCancerTrials.com also provides personalized clinical trial searches on behalf of patients.(
Proceedings from the American Society of Hematology, abstract #2820, Orlando, Florida, December, 2001)
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