September 17, 2020| By Dr. Judith N. Gorski

September is Blood Cancer Awareness Month

Living with Adult Acute Lymphoblastic Leukemia

September is Blood Cancer Awareness Month. The Leukemia & Lymphoma Society® (LLS) is a global leader in the fight against cancer and has helped advance 54 of the 64 blood cancer treatment options approved by the U.S. Food and Drug Administration since 2017. This month the LLS announced it is launching the first clinical trial dedicated solely to leukemia and lymphoma patients infected with the COVID-19 virus. As a vulnerable population, studies show between 30-60% of blood cancer patients are at risk of death if infected with the COVID-19 virus compared to patients who are cancer-free. There is still much more work to be done.

Leukemia is a cancer of the blood. It begins when the bone marrow starts to rapidly produce abnormal white blood cells called leukemia cells. There are two primary types of white blood cells: myeloid cells and lymphoid cells. Leukemia can occur in either type. In people who are affected by leukemia, the white blood cells do not function normally, meaning that they don’t aid the immune system in warding off invasions. Additionally, because of the sheer volume of these cells, they can affect the function of major organs. Over time, there aren’t enough red blood cells to provide the body with the proper amount of oxygen or platelets to clot the blood. Also, there aren’t enough normal white blood cells present to fight off infections. The risk factors include but are not limited to hereditary and environmental factors that may play a role in developing the disease; mutations in the DNA and chromosome translocation can also promote activation of oncogenes (the cancer inducing genes), which can lead to disease progression. Depending on the type of leukemia, current treatment options include single or combinations of chemotherapy drugs to destroy leukemia cells; biological or immune therapy to help the immune system recognize and attack cancer cells; or targeted therapy drugs, whereby a specific drug targets only the cancerous cells.

Leukemia is also the most common cancer in children and teens, accounting for about three-quarters of pediatric leukemia cases. Very rare, with fewer than 3,000 cases per year in US, is adult acute lymphoblastic leukemia (ALL). Adult patients present with symptoms such as fatigue, bruising, nausea and difficulty breathing; they have abnormal white blood cell counts and differential, abnormal hematocrit/hemoglobin and platelet counts and abnormal bone marrow with more than 5% blasts. Adult treatment studies are modeled on childhood ALL studies and use multiple treatment modalities, including systemically administered combination chemotherapy with CNS preventive therapy and, in some cases, cranial radiation therapy. The average length of treatment for ALL varies between 1.5 and 3 years to try to eradicate the leukemic cell population.

Recently, a colleague of mine shared the story of his battle with ALL. He was in good health, had a personal trainer, worked out at the gym—overall a healthy male in his late 50’s. He recalls the moment he started having episodes of shortness of breath performing normal everyday activities, when running up a flight of stairs, something he did effortlessly seven days a week. Like many of us so busy, he dismissed it as nothing. Coworkers insisted he have an X-ray. After a CAT scan of his chest revealed a large mediastinal mass and bloodwork results with 13% blasts, he was diagnosed with ALL. Shocked and numb, he went home and shared the news with his wife and hugged his three-year-old daughter. It would be a long and painful road back to being cancer-free. Fortunately, he was admitted to Sloan Kettering and placed under the exceptional care of Dr. Dan Douer, leading expert in leukemia and bone marrow transplantation (BMT). My colleague was a candidate for a BMT; however, weighing the benefits and the risks, he decided to follow Dr. Douer’s revolutionized protocol.

In 2014, the same year my colleague was diagnosed, Dr. Douer published Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia. (J Clin Oncol. 2014;32(9):905-911) This paper describes adolescents and young adults with ALL who had consistently demonstrated significantly longer survival when treated by pediatricians with a pediatric regimen than patients of the same age treated by oncologists who treat adults using adult regimens.  Pegasparaginase is the long-acting pegylated form of asparaginase, a bacterial enzyme that hydrolyses serum asparagine into aspartic acid and ammonia, thus depleting serum asparagine and depriving ALL cells of this nutrient. Two pediatric studies reported the favorable impact of intensive post-remission asparaginase on leukemia outcomes. The Dana-Farber Consortium 77-01 study reported that patients treated with intensive post-remission high-dose asparaginase had significantly superior outcomes compared with patients who did not receive post remission asparaginase. (Cancer Res. 1983;43(11): 5601-5607) Likewise, the POG 8704 study in T-cell ALL reported an improved 4-year continuous complete remission (CR) rate for patients randomly assigned to post-remission high-dose asparaginase versus no asparaginase consolidation (68% vs 55%). (Leukemia. 1999;13(3):335-34) These data, along with experts like Dr. Douer, catapulted the practice of pediatric regimens to adults with ALL, with upper ages ranging from 39 to 60 years; my colleague was 59.

Treatment with asparaginase is problematic in adults. The toxicity profile of the drug is unique and is not observed with any other chemotherapy agent. Asparaginase is almost exclusively used in ALL, a very rare cancer in adults, and most general oncologists who treat adults are not familiar with its usage and toxicity. Therefore, oncologists who treat adults may be reluctant to use pegasparaginase or may unnecessarily discontinue administering it because of certain adverse effects. Clinical benefit may be at risk if multiple doses of pegasparaginase are missed. Despite the fact that pegasparaginase is associated with unique toxicities, the majority are nonfatal, manageable, and reversible. This March, Dr. Douer published in Blood (2020;135(13):987-995), an article describing real-life cases of adults with ALL who were treated with pediatric-inspired regimens that incorporated pegasparaginase to illustrate the management of several pegasparaginase-associated adverse effects and guide whether and how to continue the drug. My colleague agrees the side effects were brutal and somedays wanted to “give up.” However, because of careful patient education and early detection and management of the toxicities, his dosing regimen was unchanged and efficacy was not compromised. Today he is fortunate to be in complete remission. It is unfortunate his original complaint of having difficulty breathing was likely from the mediastinal mass causing direct trauma to his phrenic nerve; as a result, he lives with paralysis to a significant part of his diaphragm. He says he may not be able to run a marathon ever again, but he is blessed that he can take a walk with his 9-year-old daughter.

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