Heather's quiet sense of humor and easy smile belie the challenges she has surmounted: chemotherapy, bone marrow transplantation, treatment of relapse nine years after transplantation, and long-term side effects of treatment. Although Heather has a very loving and supportive family, she took charge of her treatment at an early age with a disciplined sense of responsibility and sought appropriate treatment for herself when she moved from her home in Buffalo to New Jersey and then home again. Despite physical challenges, Heather married and miraculously, she and her husband, Tim, have two beautiful children of their own.
Heather's Treatment Story - CML & BMT
Chronic Myelogenous Leukemia is a disease of adults and is rarely seen in childhood. In fact, CML comprises only one percent of childhood leukemias. For this reason, Heather's oncologist was surprised to find that her bone marrow showed the characteristic finding of CML, which is the presence of the Philadelphia Chromosome noted on chromosome analysis.
Treatment of CML has radically changed since Heather was diagnosed in 1988. In 1988, patients with CML were generally treated with chemotherapy, interferon, or both prior to proceeding to bone marrow transplantation from a tissue-type matched sibling or close relative. Since then several diagnostic techniques to detect CML cells in the marrow have been developed, a new class of drugs has been developed to treat Philadelphia Chromosome positive leukemias, and the National Marrow Donor Program has been established to facilitate transplants between patients without a matched family member and matched unrelated donors.
Heather's diagnosis was made by a crude viewing of only 20 sets of chromosomes within her leukemic cells. Now the diagnosis would be confirmed with additional tests including "FISH" analysis (500 cells examined), and a molecular technique called RT-PCR that can detect one leukemic cell in 10,000 bone marrow cells. The class of drugs known as tyrosine kinase inhibitors has transformed the treatment of CML and essentially eradicated or greatly reduced the need for bone marrow transplant (BMT). Tyrosine kinase inhibitors such as Imatinib (Gleevec®) do not cure or eradicate the leukemia cells of CML; rather they inhibit the growth of leukemia cells and prevent the leukemia cells from replacing normal cells in the marrow. The drug must be taken by mouth for life as studies have shown the leukemia cells multiply quickly when patients stops taking it.
Heather was diagnosed at age 11 and initially treated with chemotherapy at Roswell Park in Buffalo, New York. After about six months of treatment, she was referred to Memorial Sloan Kettering Cancer Center for a transplant from her HLA identical sister, Heidi.
Treatment Advances Today
Were she to be diagnosed as an 11 year old in 2007, her initial treatment would be with Imatinib, a far less toxic drug than the ones she received in 1988. Since she has a matched sibling and is young, we would recommend that Heather have a BMT when she had a minimal level of leukemia cells, as measured by the newly developed molecular techniques. Today adults with CML are treated indefinitely with Imatinib or a second generation tyrosine kinase drug and do not proceed to BMT with either a related or unrelated donor unless they are unable to tolerate the side effects of Imatinib or become resistant to treatment with a tyrosine kinase inhibitor.
Heather received total body irradiation and two chemotherapy drugs, a regimen identical to one in use today. However, Heather was a pioneer as she enrolled in our first protocol to test this approach in matched siblings and received a marrow depleted of T-cells to prevent the occurrence of graft-versus-host disease (GvHD). She successfully engrafted and did not develop GVHD. Because she did so well early after transplantation, she returned to Roswell Park for her follow-up care.
In 1988, we did not know of the need to closely monitor -- every three to six months -- the marrow after transplantation for recurrent leukemia in patients with CML. With a T-cell depletion approach, patients with CML, but not acute leukemia, are more likely to relapse than recipients of unmodified, non-T-cell depleted marrow. Unfortunately, nine years after her BMT, Heather presented in full relapse with many leukemia cells in her marrow. Her closely knit family rushed her back to New York for evaluation and treatment.
In the nine years following her BMT, we and others had demonstrated that infusions of small numbers of donor T cells ("donor leukocyte infusion" or DLI) could eradicate the leukemia through a "graft versus leukemia" effect. Fortunately, Heather's matched sister, Heidi, was still healthy and willing to donate cells for Heather. But similar to how she felt when her sister donated marrow for her, Heather worried how Heidi would do donating leukocytes for her. Both did well and Heather received three infusions between May 1997 and October 1998. Three T-cell infusions were required to eradicate her CML as measured by FISH and molecular techniques. Heather has remained in remission since March 1999.
Following the T-cell infusions, Heather developed GVHD, a complication that we had avoided early on with a T-cell depleted BMT. She developed a rash and stiffness in her fingers that prevented her from playing the piano. She required treatment with immunosuppressive medications for two years. This period of time was not easy for Heather as she suffered the side effects of steroid therapy. T-cells are still the mainstay of treatment for relapse of CML following transplantation. But, it is likely that today we would also treat with Imatinib and perhaps be able to limit the number of infusions to one or two doses and, thus, avoid the development of GvHD. The potential success of this approach remains to be determined.
A Privileged Partnership
Peppered throughout treatment of leukemia and attending to her new family, Heather has met the challenges of coping with complications of her treatment, including hip replacements for avascular necrosis, cataract surgery, recurrent sinusitis, and osteoporosis.
I started this piece stating that it has been privilege partnering with Heather to optimize her oncology and follow-up care. It has been a true partnership: we are e-mail buddies. My Buck-Brown file is filled equally with subject titles "Hip Revision," "new rash-photograph attached and NEWS!!!" "Baby update" - photographs attached: Randy and Emma Grace. In "Hip Revision," Heather noted her first hip had lasted nine and a half years, boasted of her new ceramic hip, and rejoiced in having her two year-old getting her things and helping her out. There is no mention of the pain of surgery or physical therapy. In short, Heather's spirit inspires her doctors, her family, and all who have come to know her during her journey.
