CANCER GUIDE CONSULTATIONS - CASE HISTORIES Marcy Klapper Marcy Klapper was the first case I took on as a CancerGuide. She was a close personal friend for two decades. Marcy was diagnosed with Chronic Myelogenous Leukemia - CML - in March 1990. Her WBC count was over 50,000, and bone marrow tests conduced by her local oncologist in Springfield, MA confirmed Philadelphia chromosome positive CML. (She had 100% Philadelphia-positive [Ph+] cells in her bone marrow, meaning that all of her granulocytes had a specific mutation - the bcr-abl translocation - that defines the molecular biology of CML. This is a typical initial finding in CML). Marcy was a schoolteacher who lived in Northampton, MA, with her husband, a high school principal, and their three children, a daughter aged 10, a son, 8, and another daughter, 4 years old. Marcy told me her diagnosis and she and her husband asked for my help. I began conducting extensive research on CML. Her local oncologist recommended the chemotherapy drug hydroxyurea, standard first-line therapy for CML in the absence of a bone marrow match. At the time, BMT was the only chance for a cure of the disease, while chemotherapy (primarily hydroxyurea) was not expected to prolong lifespan much if at all beyond the 3-4 year life expectancy with CML. The primary effect of hydroxyurea was to bring about hematalogic remission (restoration of normal blood counts) and perhaps some transient reduction in the percentage of Ph+ cells in the bone marrow (a partial or temporary cytogenetic remission). Marcy, her family, and I shared the belief that this was not an acceptable treatment plan. Her siblings did not match her for BMT, and she put her name in the bone marrow registry, though BMT was not Marcy's first choice. She was extremely skeptical about Western medicine, in part because it had failed her older sister, who died of the same disease a decade before. (One of the strange aspects of Marcy's case is that CML does not run in families, and only 8,000 Americans each year are diagnosed, yet it afflicted both Marcy and her sister). Marcy consulted her brother, practitioner of an arcane yet revered form of acupuncture taught by a elderly Japanese Master with whom he had studied. Her brother was practicing in France and agreed to move temporarily back to the United States to treat his sister with his form or acupuncture, in which needles are not actually inserted into the skin. In my consultations with Marcy, I encouraged her to pursue treatment with her brother while also encouraging her to keep an open mind about "Western" treatments that she could use alongside his acupuncture treatment. But her brother did not approve of any Western therapies, believing that they were toxic and would conflict with his energy-balancing and host-building treatment and philosophy. I continued my research and came upon a paper by Dr. Moishe Talpaz of MD Anderson in Houston, in which human interferon alpha, a biological response modifier, had shown significant effects in CML, bringing about hematologic remissions and some cytogenetic remissions (dramatic and sometimes complete reduction of Ph+ cells in marrow) in many patients. I called Dr. Talpaz directly, and in a lengthy phone conversation, he discussed the potential of interferon in CML, and offered me soon-to-be-published data on a large group of CML patients he was treating with recombinant interferon-alpha. Approximately 80% were experiencing complete hematologic remissions and 50% were experiencing partial or complete cytogenetic remissions - the latter being the most important indicator of disease reversal. Moreover, these cytogenetic remissions appeared more durable "long-lasting" than anything seen with chemotherapy. He predicted from his data that interferon would substantially lengthening the lifespan for a healthy percentage of CML patients, probably well over half. I thought that Talpaz's story might be too good to be true, but he was so knowledgeable, and his published work so credible, that I shared my enthusiasm with Marcy. She was interested but still so committed to treatment with her brother, and so certain of his healing abilities, that she decided not to pursue interferon at that time. Over the next year, Marcy and I continued to speak and I tried not to push too hard about interferon, hoping only to convince her to keep an open mind about complementarity - she could try interferon while continuing to work with her brother. I explained that interferon was not chemotherapy but rather a biological molecule reproduced precisely through recombinant technology, and that it stimulated immune responses against leukemic cells and had other antiproliferative effects on these cells. While the mechanism of action was not completely understood, it was not a toxic killing agent but rather a form of biotherapy that could work well with a treatment designed to restore balance and harmony to her system. After many months, Marcy's WBC counts continued to rise, and about one year after her diagnosis, her counts exceeded 200,000—a dangerous level that could herald a blast crisis, the beginnings of a life-threatening lapse into progressive disease. Marcy's sister became extremely concerned, and she and I restated our hope that Marcy would consider interferon. Marcy agreed, but said that she would proceed only if her brother could be persuaded. Toward this end, I traveled to Northhampton to hold what was, in effect, a summit meeting with Marcy;s brother Doug. I presented Marcy, her husband, and Doug with papers by Talpaz about interferon for CML, including data showing that it was most likely to be effective before the disease progressed to accelerated phase or blast crisis. I was letting them know, gently but as clearly as possible, that any further delay might mean she would lose the opportunity to benefit from interferon. I spoke to Doug with as much respect and compassion as I could muster, pleading my case that inteferon and acupuncture - far from being opposed - ;could work synergistically. After a difficult few hours, he agreed, and Marcy had his blessing, even if it was ambivalent. But where would she get inteferon? Her own hematologic oncologist in Springfield was extremely skeptical; he did not think inteferon was far enough along in terms of clinical studies to merit such consideration. I wrote him a six-page letter describing the data, including Talpaz's as-yet unpublished findings and assertions. Then I found a well regarded hematologist at Albert Einstein Medical School in the Bronx, NY, who was using interferon for CML patients, and Marcy went for a consult. It was a painful experience, because the doctor told Marcy she probably would not benefit from interferon since she had 100% Ph+ cells in her marrow, and it appeared to work best in patients with "chimerism" - some percentage of Ph+ and Ph- cells. Marcy was deeply discouraged and decided not to pursue interferon there or elsewhere. I was disturbed and sat with this bad news for a few weeks before deciding to look more deeply into the issue. I went back to Talpaz's papers and read the fine print. I saw that almost all of the patients in his largely successful clinical trial has been 100% Ph+, which indicated that the Albert Einstein hematologist must have been wrong. I called Talpaz once more, and he confirmed that interferon was absolutely effective in many 100% Ph+ CML patients. (Indeed, the vast majority of CML patients are 100% Ph+ when diagnosed). When I called Marcy to explain this good news she remained skeptical, and it took several conversations over two months to re-ignite her interest in interferon. This time, I suggested, she should go to the source - make an appointment with Talpaz himself. She went to MD Anderson in Houston with her husband and found Talpaz, a cherubic Israeli gentleman with an offhanded, irreverent 'ense of humor that matched Marcy's, to be frank, charming in a gruff way, and extremely positive - yes, hopeful - in his explanations about interferon for CML. She came armed with a list of questions and a tape recorder, and she taped the entire session which lasted over an hour. Marcy was delighted by Talpaz and the hope he offered. She came home and reconnected with her local oncologist, who now seemed more amenable, and he agreed to oversee her treatment locally. Talpaz would prescribe the precise protocol and follow Marcy with regular blood tests and bone marrow biopsies, including precise PCR molecular analyses of Ph+ percentages in her bone marrow that tell whether cytogenetic remission has been achieved. In CML, cytogenetic remission is the gold standard; it tells whether the disease is being reversed at its core, not just symptomatically. Marcy began interferon in July 1991, taking 10 million units 3 times per week by intramuscular injection. She experienced flu-like symptoms for two weeks which remitted thereafter. Her most significant side effect in the first 6 months was thrombocytopenia, which required her dosage to be cut in half to 5 million units 3x per week. I encouraged Marcy not only to continue working with Doug, but also to maintain her low-fat diet replete with soy products and sea and other vegetables, to meditate, and to pursue other herbal treatments. She did all of this and much more, following her own healing path without any direction from me or anyone else. (When she began to pursue healing paths that her brother did not entirely approve of, I saw this as a positive sign.) She rediscovered her Jewish roots and began a practice of prayer and Jewish ritual for the first time in her life. She had a meeting with Yoshi Donden, the Dalai Lama's personal physician, and received Tibetan herbal remedies that she took for several years. And she continued her acupuncture treatments with her brother. Within weeks of starting interferon her WBC counts dropped dramatically. Within 4 months, her counts dropped from 210,000 down to 4000 - which is in the normal range - a complete hematologic remission. With her dose adjustment her platelets returned to the low end of normal. After six months, her Ph+ count dropped from 100% to 80%. After approximately a year-and-a-half of interferon treatment, her Ph+ count plummeted to 5%. By this gold standard, she was very close to complete cytogenetic remission. Leukemic cells had not been completely eradicated from her body, but clinically this did not seem important - Dr. Talpaz believed that her CML had been thoroughly tamed and he did not expect an imminent relapse. Nor was there to be a relapse. Marcy remained in complete hematologic and near-complete cytogenetic remission for the next ten years. During that time, her Ph+ percentage ranged between 5% and 15%, or, put differently, the percentage of healthy granulocytes in her bone marrow ranged between 85%-95%. In her decade of remission, Marcy was physically healthy, if at times fatigued from the interferon. (Incidentally, in 1994 inteferon was established as the first-line treatment for chronic-phase CML.) The other significant long-term side effect was intermittent manic depression, which was partially caused and certainly exacerbated by the interferon, which in a small percentage of cases has adverse neurotoxicity. This was successfully treated with lithium and later with SSRI medications. The combination of psychospiritual healing approaches and medication enabled Marcy to remain active, functional, and in good spirits most of the time. She never missed any significant time as a schoolteacher, and she and her family moved to Martha's Vineyard in 1996, where they became the hub of a vibrant community of family and friends. In mid-2000, however, Marcy experienced her first serious health crisis since she began taking interferon. Her platelets crashed, going down at one point to 1000 - which Dr. Talpaz later described as "life-threatening thrombocytopenia." She had to stop taking interferon immediately and began prednisone to restore her platelets. After some confusion and differing opinions among doctors, Marcy was diagnosed by Talpaz with immune thrombocytopenia caused directly by interferon, and she was told she would have to remain off it indefinitely. This raised the issue of whether she could now safely discontinue interferon or whether she would suffer a CML relapse as a result. It appeared that she had no choice but to wait and see, although Talpaz explained that a new drug, STI 571, offered new hope for CML and that she would be a candidate if her disease began to progress after stopping interferon. My research on STI-571, a signal transduction inhibitor that interferes with a protein (EGFR tyrosine kinase) that promotes the growth of Ph+ leukemia cells, certainly concurred that it was an enormously promising agent. It was developed and studied by Dr. Brian Druker of the Orgeon Health Sciences Medical Center, who collaborated with Talpaz and several others on the initial multi-center clinical trials. After being off interferon for several months, Marcy had a bone marrow test that showed her Ph+ cells had returned to 100%. It proved that interferon had indeed kept her disease in check for a decade, and that now she needed another treatment to prevent the inevitable blast crisis and disease progression that would occur in time. Research on STI-571 was so promising that clinical trials were springing up around the country - including at the Dana-Farber Cancer Center in Boston. Marcy was referred by Talpaz to the lead investigator at Dana-Farber, and in February of 2001 she was accepted into a clinical trial there. She began taking STI-571 in March and has continued since them. In May of 2001, STI-571, under the commercial name Gleevec, was approved by the FDA on a fast-track as a new treatment for CML - the quickest approval for any cancer drug in history. On news magazine covers and throughout the media, it was hailed as a major breakthrough in cancer treatment, heralding a new approach in which low-toxicity oral agents that target the internal signaling pathways in cancer cells vanquish tumors with little damage to normal tissues. Marcy takes four Gleevec pills in the morning and she has no side effects whatsoever after five months of treatment. Her blood counts are completely normal and she awaits results from her first bone marrow biopsy, but she and her doctors are very hopeful since the vast majority of CML patients on Gleevec are doing extremely well, including many with disease far more advanced than Marcy's when she began taking the drug. Marcy's case exemplifies the possibilities of cutting-edge conventional treatments combined with complementary modalities, and it affirms the principle that cancer treatments, such as interferon, may not eradicate every cancer cell but they can make cancer a manageable disease that remains dormant. Moreover, this prolonged dormancy may keep patients healthy until an even more effective therapy becomes available. In Marcy's case, that breakthrough has been Gleevec, which became available just when interferon had run its course after a decade of remission. Gleevec, her host-building complementary treatments, and her faith, offers her the prospect of many more decades of good health.