Bone marrow transplant as frontline treatment in acute leukemia
Why one develops leukemia remains unknown. The possible factors include viruses, prior treatment with concomitant chemotherapy and radiation, and exposure to chemicals such as benzene. However, these associations comprise only a small percent, and majority gets the disease without any underlying cause.
Acute leukemia is not limited to any age bracket, occurring anytime from infancy to senility. Though it only comprises approximately one-third of cases of childhood cancer, the same is not true for adults. Leukemia is generally classified on the basis of the cell of origin: Acute lymphoblastic leukemia (ALL) is more common in children while acute myeloid leukemia (AML) in adults. Distinguishing one from the other is important, as both treatment and survival of the patient will differ.
The disease occurs when there is an arrest in the development of our red blood cells, white blood cells, and platelets. The bone marrow or bulalo produces these cells in our blood. The red blood cells (RBC) carry the oxygen we inhale and transport it to all the tissues in the body; the white blood cells help fight infection; and the tiny platelet particles form blood clots to help stop the bleeding of cuts or wounds. These three originate from the stem cell, which has the capacity to regenerate. All three also undergo different stages of maturation, and they eventually leave the bone marrow to enter the blood vessels.
When an arrest in these cells’ development occurs, there is an increase in the number of young cells, called blasts, to more than 20 percent from the normal three to five percent. This malignant clone of blast cells is referred to as acute leukemia. The leukemic or blast cells continue to divide and will ultimately occupy much of the place in the bone marrow, leaving less room for the RBC and platelets to divide.
This occurrence gives rise to leukemia’s symptoms which include anemia or a drop in hemoglobin, manifested by shortness of breath, fatigue, difficulty in breathing, dizziness, and pallor. A drop in platelet count or thrombocytopenia causes bruises and at times, spontaneous nose or gum bleeding. Tiny red dots called petechiae also appear. Fever with concomitant infection happens because the white blood cells do not function well. These non-specific symptoms should alert one to seek consultation. Typically, a complete blood count or CBC is done and often reveals anemia, thrombocytopenia, and a high or low WBC count. Blast cells, more often than not, may be seen in the blood, which further increases the suspicion that one has acute leukemia.
The treatment of acute leukemia consists of two phases, all requiring chemotherapy whether in the intravenous or tablet form. Regimens with different combinations of chemotherapy drugs and schedules are used. The goal of the induction phase is to eradicate the leukemic or blast cells. The most feared complications during this time are infection and bleeding. Bacterial infection usually comes from the body of the patient because the immune system is not functioning and natural barriers that line the intestines, respiratory and urinary tracts have been damaged by chemotherapy.
The skin can breed bacteria that can enter the blood stream through tiny cracks in the skin. It is also during this time that the patient will require red blood cell and platelet transfusions because the bone marrow is empty and not producing any cells. It will take approximately three weeks for the bone marrow to regenerate and produce cells. If complete blood count and bone marrow biopsy and aspirate tests do not show leukemia cells after, then the patient is in remission. Approximately 60 to 80 percent of patients will go into remission.
For post remission therapy, more chemotherapy is administered to eliminate any residual leukemia. But that alone may not be enough. There are certain features that can warn doctors that a type of leukemia is aggressive, such as a very high WBC on diagnosis or several cycles of chemotherapy to achieve remission. Chromosome analysis or cytogenetics is the single most important factor for predicting remission rate, relapse, and survival, and can stratify leukemia into three groups: favorable, intermediate, and poor.
Those with favorable-risk cytogenetics may do well with chemotherapy alone — most children with ALL and 20 to 30 percent adult AML fall in this group. Long-term disease- free survival rates may exceed 60 percent in these patients. On the other hand, those with poor-risk cytogenetics have a high risk of relapse and a dismal five-year survival of five percent.
An allogeneic bone marrow transplant, with stem cells harvested from a matched sibling, upfront is the best option. Those with intermediate-risk cytogenetics have the option of proceeding to chemotherapy or allogeneic bone marrow transplant if the patient has a matched sibling. With chemotherapy alone, these patients have a five-year survival of 20 to 40 percent, while patients who undergo the transplant in first complete remission have a long-term disease-free survival of 60 percent.
Another alternative for those without a matched sibling is to proceed with an autologous stem cell transplant. In this situation, the patient’s own stem cells are harvested, stored, and infused later during the transplant. Current data show a disease-free survival of 40 to 60 percent. In our experience, 11 patients with acute leukemia in first complete remission had a bone marrow transplant from a full-matched brother of sister. All are alive and doing well. One of the survivors is now five years post-transplant.
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Dr. Francisco Lopez is the head of the Bone Marrow Transplant Unit of the
