LEUKEMIA
Assistant
Professor of Medicine
Director and Attending Physician
Mini-Allogeneic Bone Marrow Transplantation
Division of Oncology
New York Medical College
For
detailed therapy information, please visit www.zaaci.org
What
is Leukemia?
Leukemia
is a form of “blood cancer”. It is the result of uncontrolled growth of
blood cells, i.e., red cells (RBC), white cells (WBC), and platelets. Normally,
the three populations of above-mentioned blood cells are mainly made in the bone
marrow of sternum, and pelvic
bones. There are precursor cells,
so-called “stem cells”, in the bone marrow for RBC, WBC, and platelets. When
genetic changes occur in the DNA sequences in the precursor cells, uncontrolled
growth may take place, resulting in the leukemia.
a.
Acute myeloid leukemia (AML): This is the most common type of acute
leukemia in adults. There are seven different subtypes, M1 through M7
b.
Acute lymphoid leukemia (ALL): This type is most common in children.
There are three subtypes: L1, L2,
and L3. Each type can be a T- or B- cell in origin.
c.
Acute undifferentiated or biphenotypic leukemia: the leukemia cells in
this class can not be assigned to the above two types.
a.
Chronic myelogenous leukemia (CML): there are three different phases,
including chronic phase, accelerated phase, and blast crisis phase.
b.
Chronic lymphocytic leukemia (CLL): there are different stages of CLL,
depending upon lymph node involvement, anemia, low platelets, and spleen
involvement.
Patients with leukemia frequently present with anemia, low platelets counts, bleeding, and infection. From time to time, patients may be found to have spleen or lymph node enlargement on physical examination. Not infrequently, patients may have persistent bleeding after minor surgery, such as tooth extraction. A clear diagnosis is based upon peripheral blood smear, bone marrow evaluation, flow cytometry study, and cytogenetic study. These should be done for every patient. The flow cytometry study is routinely done to assist classification of the leukemia. The cytogenetic study is particularly important for predicting prognosis. AML with the cytogenetic changes, t(8;21), t(15,17), and inv(16), are considered to have good prognosis. Deletion of chromosome 5, 7, or addition of chromosome 8 are considered to be poor prognostic factors, whereas normal or other type of cytogenetic changes are intermediate. ALL with t(4;11) or t(9;22) have poor prognosis.
In general, there are different phases of treatment for acute leukemia, including induction, consolidation, maintenance.
a. AML: most commonly used chemotherapy drugs are cytarabine and idarubicine, and “7+3” is still the standard way of giving the drugs outside of a clinical study. A repeat of bone marrow evaluation is routinely done around day 14 to assess the effect of the chemotherapy. Another bone marrow evaluation is usually done at day 28 to document whether the leukemia is in complete remission, in other words, whether the leukemia has been controlled to the extent that no evidence of leukemia can be identified by routinely used clinical studies. Consolidation chemotherapy is usually given a week or two after patient has recovered from chemotherapy. Maintenance chemotherapy is not routinely used for AML. Two new advances in the therapy of AML-M3 (acute promyelocytic leukemia) initially originated from China. All trans-retinoic acid and arsenic trioxide have been proven to increase rate of complete remission with significantly less toxicity and fewer toxic death in the therapy of M3.
b.
ALL: The therapy of ALL is considerably more complicated and less
standardized. There is still no uniformed accepted “standard therapy” for
ALL. Vincristine, prednisone, cyclophosphomide, daunorubicine, and asparaginase,
are commonly used for induction. High dose cytarabine and mitoxantrone are being
studied for induction therapy. Maintenance therapy for at least two years is
usually given. Administration of chemotherapy to the central nervous system
through the spinal fluid (intrathecal chemotherapy) is routinely done.
Methotrexate and cytarabine are the commonly used drugs. Prophylactic radiation
therapy is not done any more due to unproven benefit and long-term
complications. Lymphoblastic lymphoma is considered to be another form of ALL,
and treated the same way. Mature B-cell ALL (Burkitt’s ALL, L3) is treated
differently from other type of ALL, usually involving the use of high dose
methotrexate. Children with ALL do much better than adults, due to the different
biological behavior and characteristics of their leukemia cells.
There
are Allogeneic BMT and autologous BMT. Allogeneic means from a different person,
whereas autologous means from self. Allogeneic BMT is much more valuable. There
are six different types of HLA ( human leukocyte antigen) antigens usually
tested, the so-called “HLA
typing”. If two individuals have
all six HLA matched, it is considered to be HLA identical. Siblings (brothers
and sisters) have a 25% chance to be HLA-identical. In the Caucasian population,
due to the large database from HLA bank, there is roughly a 70% chance for any
Caucasian patient, particularly the European descendent,
to have a HLA-identical donor. For young patients with CML, allogeneic
BMT is the preferred treatment, and roughly 75% of those patients may be cured.
Interferon therapy should be stopped at least 3 months before BMT. Allogeneic
BMT is usually not advisable for patients who are older than 55 years old due to
the significantly higher possibility of treatment-related death. Transplantation
of growth factor-mobilized peripheral blood stem cells may become more and more
popular due to the ease of procurement and rapid engraftment. However, long-term
sequelae are still unclear. Mini-allogeneic BMT with milder form of treatment is
under intensive clinical study and may be used for therapy of patients who are
older than 55 years old and /or have other significant diseases that preclude
them from conventional BMT.