Score two for medical evolution

I recently saw a patient with splenomegaly. The patient, a 36-year-old man with pancytopenia, pneumonia and splenomegaly was very nervous when I entered the room. I could see his wife was also in a state close to panic. I wasn’t sure if they were going to jump out of the window from fright or remain seated. They stayed put.

I explained, as all of us do frequently in our professional lives, that the way out of the unknown was to do a bone marrow test. Doing this was the way to make a diagnosis and proceed with the proper treatment. I thought that this patient’s differential diagnosis at this point was either hairy cell leukemia or splenic lymphoma. As there were no blasts on the peripheral smear, I did not think he had acute leukemia. I proceeded with his bone marrow. Flow cytometry showed that the cells were monoclonal kappa light chain restricted and positive for CD19, CD20, CD11c, and CD103. CD5, CD10, and CD23 were negative. It was very typical of hairy cell leukemia. I returned the next day to explain the results to the two of them.

Arthur Topilow

I reviewed the treatment options for hairy cell leukemia before walking into the room. The patient’s wife was, by this time, a basket case. Of course, my advantage was that the patient had an illness for which we expect a good response with current treatments. I described the management options with the patient and his wife, the rationale for the treatment and the expected outcome. I must have done a good job, since the patient decided that even though I was out of his insurance network, he wanted me to treat him. I was flattered. He needed a little more encouragement to wait calmly, putting the treatment on hold until his pneumonia resolved. He then underwent a seven-day course of cladribine without problems. He was discharged, but then readmitted a week later with fever. This was successfully treated with antibiotics. His blood count normalized, his splenomegaly resolved and there have been no signs of his illness for the past 16 months.

Treating hairy cell leukemia

Hairy cell leukemia is rather rare. There are only 600 to 800 new cases per year in the United States. I reviewed in my head the cases I had treated over the years, their modes of diagnosis and their treatments.

My first patient was in 1973. I was Major Topilow then, stationed at Fort Dix during the last days of the Vietnam War. The patient, a woman in her late 50s, seemed to have a somewhat unusual case of CLL. She presented with mild leukopenia and relative lymphocytosis. Her platelet count and hemoglobin were normal. She had no adenopathy, but her spleen was enlarged to palpation. I did her bone marrow, which showed some lymphocytic infiltration. I thought she had CLL, and arranged for consultation at Walter Reed Army Medical Center. She returned to my clinic several weeks later and announced, “I have hairy cell leukemia.” I was somewhat surprised and a little embarrassed that neither our pathologist nor I had made the diagnosis. In 1973, the only diagnostic test was the blood smear. Tartrate resistant acid phosphatase, a confirmatory test for hairy cell leukemia, had just been described. Cladribine and pentostatin had not yet been released. I saw the patient a few more times in our clinic. She was not treated at the time of diagnosis and I do not know her follow-up.

Ten years later a woman in her 60s came to me. She was status postsplenectomy for hairy cell leukemia. Over the next 20 years, I continued to see her. She died of heart disease, never having had additional problems with her leukemia.

Eighteen years ago Mr. J came to the office. A retired physical education teacher, he had marked pancytopenia and mild splenomegaly. He wound up in the hospital with severe anemia, and required multiple units of blood. Flow cytometry was not yet in general use. After intensive study and many frustrating days, a diagnosis of hairy cell leukemia was finally made. He was treated with cladribine and is still disease free. At age 91, he goes to the gym five days a week to work out.

An evolving practice

These four cases show the evolution of the progress in the diagnosis and treatment of hairy cell leukemia. The disease was originally known as histiocytic leukemia, malignant reticulosis or lymphoid myelofibrosis in publications dating back to the 1920s, and later was named leukemic reticuloendotheliosis. Its common name, which was coined in 1966, is derived from the appearance of the cells under the microscope. Flow cytometry allows for diagnosis certainty and cladribine gives excellent results with a complete response of 82%, a partial response of 18% and a 100% 10-year survival. Splenic radiation and surgical splenectomy is pretty much a thing of the past. We have two excellent drugs that may well be curative. So we can all enjoy a real medical advance in treating this condition.

I described my hairy cell leukemia evolution saga to my wife, Judy, a pediatrician who was a medical school classmate. She never sees hairy cell leukemia, but she reminded me of the evolutionary process that has occurred over the years in the diagnosis and treatment of acute lymphatic leukemia in children.

In private practice for almost thirty years, Judy diagnosed two cases while covering “sick only” children weekend visits in her office. The first was about 25 years ago in a visiting Jersey shore summer patient aged about 3 years old. Marked pallor and organomegaly led quickly to the diagnosis of ALL in this patient who my wife had never seen before. By that evening, the patient was safely ensconced with the pediatric hem/onc team at Mt. Sinai in Manhattan. Ten years later Judy answered a follow-up survey from Mt. Sinai inquiring as to the whereabouts and medical condition of the patient. Unknown was the answer, as the girl had not been a regular patient in Judy’s practice. However, a few summers ago, Judy spent another Sunday in her office. After examining a not too sick toddler, the child’s very pregnant mother said, “You don’t remember me, do you?” There was Mt. Sinai’s follow-up in the flesh, much to Judy’s delight.

On another occasion a few years ago, Judy and I were both delighted when we visited several couples in their late 20s at a fancy wedding at our local synagogue. Judy recognized two or three people at the table as her former patients, but we both failed to recognize another former patient — a beautiful young woman, now a social worker, married with two children. She had been diagnosed with ALL early in her freshman year at college. We both remember from our own childhood, friends who died in a matter of months with leukemia.

When she brings her children to Judy’s office, my wife always asks the sister of a Washington lawyer how her brother is doing. He became Judy’s patient at about age 15, after he had finished his therapy for ALL, and had a testicular biopsy. He’s fine, his sister regularly replies, as are his wife and the children.

In the office just a few Saturdays ago, pallor and splenomegaly once again led Judy to suspect leukemia in a five-year old. This was quickly confirmed as ALL, with no high-risk indicators. When the father queried Judy about the long-term prognosis for his daughter, she told him that the answer to that question could best be answered by the hem/onc team, but she did not hesitate to tell him about the two patients she failed to recognize so many years later, as well as the Washington lawyer. Her patient’s father understood.

What can I say? Sometimes it’s nice to swap happy or potentially happy ending stories with an intimate colleague.

Arthur Topilow, MD, FACP, is in private practice at Atlantic Hematology & Oncology in Manasquan, N.J.

Judith F. Topilow, MD, FACP, is in private practice with pediatrics in Wayside, N.J. She is Codirector of the Muscular Dystrophy Association Clinic in Monmouth County, N.J.

For more information:

• Yam LT, Li CY, Lam KW. Tartrate-resistant acid phosphatase isoenzyme in the reticulum cells of leukemic reticuloendotheliosis. N Engl J Med. 1971;284:357-60.
• Seshadri RS, Brown EJ, Zipursky A. Leukemic reticuloendotheliosis. A failure of monocyte production. N Engl J Med. 1976;295:181-184.
• Schrek R, Donnelly WJ. “Hairy” cells in blood in lymphoreticular neoplastic disease and “flagellated” cells of normal lymph nodes. Blood. 1966;27:199-211.
• Else M, Ruchlemer R, Osuji N, et al. Long remissions in hairy cell leukemia with purine analogs: a report of 219 patients with a median follow-up of 12.5 years. Cancer. 2005;104:2442-2448.