DOCTOR'S VIEW ARCHIVE

Leukemia in the Family

Medical Author: Frederick Hecht, MD, FAAP
Medical Editor: William C. Shiel Jr., MD, FACP, FACR

(This Doctor's View was written by one of MedicineNet.com's Medical Editors, who is a grandfather, father, and doctor.)

Nightmarish News

Sometimes, I write poems when I have something on my mind that I find hard to put in words, but which somehow needs, I think, to be recorded in black and white. So, on February 18th I wrote this short poem. It is not a great poem. It may not even be a halfway decent poem. I don't know. I just needed to write it. Here it is:

Tania, our lives will not be
the same again since
you were found not to be
a healthy high school kid
but to have leukemia.

I still am too shaken
to write much about it
but you are strong
and we will be, too.

Tania is our granddaughter. She is our firstborn grandchild.

Her dad, my son Rick, had called me. He had cried on the phone and told me what was happening. To let my wife know the gist of the conversation, I wrote on a pad of paper: "Tania is very sick." I underlined "very."

Rick, who is a physician, said he had been working at home when Tania told him she had a funny rash and asked if he would look at it. Rick looked. He saw there were petechiae (tiny red spots due to bleeding into the skin). Tania had complained of feeling tired for several weeks, but what high schooler hasn't? She also had somehow picked up some bruises. He immediately called Tania's pediatrician, who saw Tania during her lunch hour.

When Rick had called me, he was still waiting for the results of the blood test that had been done on Tania. But he said quietly and with incredible sadness: "I know too much. She's got leukemia." I talked with Rick about other possible diagnoses, disorders not as serious as leukemia, but I knew that he was almost surely right, and he was.

Starting to Cope

To begin to face Tania's illness, I turned to ways I have used over the years to cope with very upsetting health events. One way is to intellectualize a situation. I put together an entry on Tania's disease -- acute promyelocytic leukemia (APL) -- for MedTerms.com, the online Medical Dictionary I edit for MedicineNet.com. The entry is meant to be for the intelligent reader, not for physicians or others who are experts in the field. Here is how it reads:

Acute promyelocytic leukemia: Commonly called APL, a malignancy of the bone marrow in which there is a deficiency of mature blood cells in the myeloid line of cells and an excess of immature cells, called promyelocytes. APL is due to an exchange of chromosome material (translocation) between chromosomes 15 and 17, which is symbolized t(15;17). This translocation is not a mere marker of APL. It is the cause of APL.

APL was first recognized as a distinct disease entity in 1957. It accounts for 5 to 10% of cases of acute myeloid leukemia (AML). APL most commonly affects young adults. APL is considered a type of AML and is classified as the M3 variant of AML in the internationally accepted French-American-British (FAB) Classification.

The signs and symptoms of APL are nonspecific and include fatigue (feeling tired), minor infections, or a tendency to bleed. There is usually low levels of red blood cells (anemia), low levels of the granulocytes and monocytes (types of white blood cells that fight infections), and low levels of platelets (which are needed for blood to clot normally). When all of these bloods cells are diminished in number it is referred to as pancytopenia. Patients with APL may require blood and/or platelet transfusions.

APL is consistently associated with a disorder that resembles (but is not identical to) disseminated intravascular coagulation (DIC). In APL, there is a pronounced tendency to hemorrhage (bleeding). The bleeding tendency can manifest itself as little bleeding spots (petechiae) in the skin or elsewhere, small bruises, nose bleeds, bleeding in the mouth, blood in the urine, and bleeding from venipuncture and bone marrow sites. In girls and women who are menstruating, excessive irregular menstrual bleeding may occur. The bleeding tendency may precede the diagnosis of leukemia by 2 to 8 weeks.

Now, on the technical side: The t(15;17) translocation in APL is the result of two chromosome breaks; one in chromosome 15 and the other in chromosome 17. The break in chromosome 15 disrupts the promyelocytic leukemia (PML) gene, which encodes a growth suppressing transcription factor. The break in chromosome 17 interrupts the retinoic acid receptor alpha (RARa) gene, which regulates myeloid differentiation. The translocation creates a PML/RARa fusion gene. It produces a chimeric protein that arrests the maturation of myeloid cells at the promyelocytic stage. This reduces terminal cell differentiation, which, in turn, leads to the increased proliferation of promyelocytes.

The treatment of APL differs from that of all other forms of AML. Most APL patients are now treated with all-trans-retinoic acid (ATRA). ATRA is a form of "differentiation therapy." It activates the retinoid receptor RAR and causes the promyeloctes to differentiate (to mature), which deters them from proliferating (multiplying). ATRA induces a complete remission in about 70% of cases.

APL patients are then given a course of "consolidation chemotherapy," which is likely to include cytosine arabinoside (Ara-C) and idarubicin. The combination of ATRA + chemotherapy permits about 95% of patients to achieve remission. In the small percentage of patients who relapse after remission, treatment may include arsenic trioxide.

The advent of ATRA therapy revolutionized the treatment of APL and markedly improved the prognosis (the outlook). However, ATRA can cause serious side-effects including fever, respiratory distress, and hypotension (abnormally low blood pressure).

In sum, APL is a form of acute myeloid leukemia that is caused by a specific chromosome translocation t(15;17). APL is associated with a characteristic cellular picture and is classified as M3 in the FAB Classification. This form of leukemia responds favorably to treatments including retinoids, chemotherapy, and, most recently, arsenicals.

Next

I plan to let you know how Tania is doing by providing you with updates on her progress. I will try to let you know, too, how we (and perhaps others in the family) are coping with Tania's illness.

To read the follow-up to this story about Tania, please read Coping with a Bad Disease - Community Counts

Last Editorial Review: 10/5/2006