Stem-cell transplants help beat lymphoma
3 February 2004. Related: Coinfections and complications, Cancer and HIV.
Sean Hosein, CATIE News
Partly because of their weakened immune systems, people with HIV/AIDS (PHAs) are at increased risk for certain tumours such as non-Hodgkin’s lymphoma and Hodgkin’s lymphoma. These tumours occur when cells of the immune system, mostly B cells, begin to multiply abnormally. Signs/symptoms of lymphoma can include unexpected tiredness, unintentional weight loss, fever, night sweats, swollen lumps in the neck, groin, or under the arms.
To help make a diagnosis of lymphoma, several procedures and tests are needed, including detailed pictures from inside the body using CAT scans or MRIs, blood tests, and biopsies of the tumour.
Lymphoma and HAART
In the time before highly active antiretroviral therapy (HAART) became available in high-income countries, the chances of survival after a diagnosis of AIDS-related lymphoma were low. Even with anti-cancer therapy, the average PHA survived for about six months. Now that HAART is available, survival after a diagnosis of lymphoma has been extended. In one study from France, researchers found that, on average, survival in the time of HAART rose to about 20 months after a lymphoma diagnosis. Moreover, researchers are testing new anti-lymphoma regimens, such as EPOCH, which appear to result in high rates of remission. For more details about EPOCH, please see CATIE’s TreatmentUpdate 136 available at:
http://www.catie.ca/tu.nsf
While this statistic is encouraging, the fact remains that some PHAs with lymphoma only experience a partial remission or may not go into remission when first treated for cancer. To deal with this situation, researchers at several Italian hospitals have been testing a combination of stem-cell (CD34+) transplants and high-dose chemotherapy in 16 PHAs with lymphoma. Their results, published in the 1 December issue of the Journal of Clinical Oncology, suggest that these treatments can help some PHAs recover from cancer when first-line chemotherapy fails.
Why transplant stem-cells?
In addition to damaging tumours, chemotherapy damages the bone marrow – the site of blood cell production. So the doctors in this study came up with the idea of giving a stem-cell transplant to the subjects. Why stem-cells? Most cells in the body are specialised, for example, nerve cells, liver cells, skin cells and so on. But stem-cells are unspecialised cells that can turn into other types of cells. In the case of CD34+ stem-cells found in the blood, these can migrate to the bone marrow and turn into cells that specialise in producing other blood cells. By giving patients a transplant of their own stem-cells (collected before chemotherapy), doctors can then use a higher-than-normal dose of chemotherapy to achieve more intensive anti-cancer effects and not greatly worry about bone marrow damage in their patients. This combination of high-dose chemotherapy and stem-cell transplants is used in HIV-negative cases of lymphoma that do not respond to chemotherapy alone.
Before receiving high-dose chemotherapy, patients are given injections of the bone marrow stimulant G-CSF (granulocyte-colony stimulating factor, filgrastim, Neupogen). A few days later, stem-cells are collected from the blood and stored. After chemotherapy, the stem-cells are infused intravenously and they migrate to the bone marrow where they help it to recover and resume producing healthy blood cells.
Study details
Researchers recruited subjects between September 2000 and April 2003. All had AIDS-related lymphoma and had not experienced sustained remission with prior chemotherapy. The profile of the 16 subjects (two female, 14 male) at the start of the study included median age 39 years and CD4+ count 236 cells/mm3. Fourteen subjects were using HAART.
Upon entering the study, subjects received a course or two of normal-dose chemotherapy. The purpose of this was to assess if their tumours would respond to the treatment. If tumours did respond, this chemotherapy served to shrink them prior to exposure to much higher doses of chemotherapy. Once their bone marrow recovered from this round of chemotherapy, stem-cells were collected. At least one month after stem-cells were collected, subjects then received high-dose chemotherapy for a week. The drugs used for the high-dose regimen were carmustine, cytarabine, etoposide and melphalan.
Stem-cells were re-infused into subjects and one week after chemotherapy began, subjects were given the bone marrow stimulant G-CSF. In addition, doctors also prescribed several medications to suppress the development of bacterial, fungal and viral infections. All subjects remained on HAART while in the study.
Results
Six of the 16 subjects in this study did not receive a stem-cell transplant. Three subjects, two of whom had less than 100 CD4+ cells, died from rapidly worsening lymphoma. The bone marrow of three subjects was unable to produce stem-cells despite stimulation with G-CSF.
The research team reported initial results from nine of the 10 subjects (the 10th patient wasn’t enrolled for a long enough time). Seven patients had a complete response (tumours disappeared) and two had a partial response (tumours shrank but did not disappear). About one year after having received a stem-cell transplant, six of the nine subjects remained alive. Most subjects experienced moderate or severe nausea/vomiting, diarrhoea and inflammation inside their mouths.
Because chemotherapy weakens the bone marrow, levels of disease-fighting cells are temporarily reduced and it is not uncommon for cancer patients receiving chemotherapy to develop infections. In this study, two subjects developed fungal infections in their throat and two subjects developed shingles.
Although CD4+ counts fell after high-dose chemo (to an average of 93 cells), by the sixth month of the study they rose to an average of 183 cells. Except for a few days when subjects stopped taking HAART because of side effects from chemotherapy, the average viral load remained below the 50 copy mark.
The researchers noted that six of the 10 subjects remained free from lymphoma for one year after receiving high-dose chemotherapy and a stem-cell transplant. Although the researchers found the results of this study promising, they caution that additional studies with longer monitoring times are needed to confirm and extend their results. Nonetheless, they suggest that high-dose chemotherapy can safely be given to HIV positive people with lymphoma. Although their research was about “salvage” therapy, because of the promising results the research team suggests that high-dose chemotherapy and stem-cell transplants be considered for use earlier in the course of AIDS-related lymphoma, as has been suggested for HIV negative people with lymphoma.
References:
- Breen EC, Boscardin WJ, Detels R, et al. Non-Hodgkin’s B cell lymphoma in persons with acquired immunodeficiency syndrome is associated with increased serum levels of IL10, or the IL10 promoter -592 C/C genotype. Clinical Immunology 2003 Nov;109(2):119-129 .
- Besson C, Goubar A, Gabarre J, et al. Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy. Blood. 2001 Oct 15;98(8):2339-44 .
- Re A, Cattaneo C, Michieli M, et al. High-dose therapy and autologous peripheral-blood stem-cell transplantation as salvage treatment for HIV-associated lymphoma in patients receiving highly active antiretroviral therapy. J Clin Oncol. 2003 Dec 1;21(23):4423-7 .
- Zinzani PL, Tani M, Gabriele A, et al. High-dose therapy with autologous transplantation for aggressive non-Hodgkin’s lymphoma: the Bologna experience. Leukemia & Lymphoma 2004;45(2):321-326.
Copyright © 2003 – Treatment Update. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Community AIDS Treatment Information Exchange, Suite 420 – 517 College Street, Toronto, On M6G 4A2 Canada