BETHESDA, Md. The number of HIV-positive children contracting AIDS-related malignancies has significantly climbed worldwide over the last decade, posing new challenges to doctors who now must treat their patients for two life-threatening diseases, according to two studies.
Of the 7,629 children diagnosed with AIDS in the United States between 1981 and 1996, 156 (2.04%) had a cancer as their AIDS-defining disease. Fifty were found to suffer from Burkitt's-like non-Hodgkin's lymphoma (NHL), by far the most common malignancy found among HIV-positive American children tested. Forty-eight suffered from immunoblastic NHL and 30 from central nervous system NHL. Kaposi's sarcoma, rare among children when compared with HIV-infected adults, was found in 28 children.
The study's authors noted that these figures underrepresented the true numbers of pediatric AIDS-related malignancies because the development of the malignancy after the diagnosis of AIDS has been made is not specifically reported.
"The decision to treat a malignancy in a child with HIV infection must be guided by the stage of the cancer as well as the patient's overall performance," said Brigitta U. Mueller, MD, assistant professor of pediatrics at Harvard Medical School. "If treatment is started by the doctor, it should be with the intention of curing the malignancy, of course, but it is also important to incorporate antiretroviral therapy into the child's treatment plan."
Mueller said this is important because the cancer therapy will only benefit the child if the clinical manifestations of HIV infection can be controlled and disease progression avoided. This is a hard balance to strike, she said.
"It's a delicate process because of the many side effects of treatment and because both diseases can be so physically and emotionally draining on the child and family," she said. "[Children with AIDS and cancer] pose a whole host of new medical and pharmacologic problems that we are now only beginning to deal with."
Currently, of the 11 AIDS-controlling drugs on the market, only five are indicated for pediatric use.
Mueller said that published treatments for HIV-associated NHL range from the very intense to no treatment at all. Most protocols concerning HIV-infected patients are not specific but rather "ad hoc" modifications of standard protocols. Most do not provide guidelines regarding management of HIV disease during chemotherapy and limited pediatric data is available.
Mueller suggested that therapeutic principles for treating children with AIDS and cancer should include dose-intensive chemotherapy of limited duration, avoidance of cardiotoxic and neurotoxic agents, awareness of potential drug interactions and comprehensive support care including psychosocial support.
Treatment of NHL in children with HIV has also been complicated by the high incidence of infectious disease and myelosuppression that are part of being HIV-positive. The Pediatric Branch and the HIV and AIDS Malignancy Branch of the National Cancer Institute are currently investigating a protocol that includes three cycles of cyclophosphamide (Cytoxan, Bristol-Myers Squibb) and methotrexate, as well as intrathecal methotrexate and cytarabine (Cytosar-U, Pharmacia & Upjohn). The protocol also includes granulocyte colony-stimulating factors to shorten the duration of neutropenia, as well as concurrent antiretroviral therapy with zidovudine (AZT, Retrovir, Glaxo Wellcome) and didanosine (ddI, Videx, Bristol-Myers Squibb). According to the study, these short but dose-intensive regimens have been found to be fairly well-tolerated by the patient.
"To date, nine patients with 10 tumors [one patient had two different tumors] have been treated with this therapy," Mueller said. "Seven patients achieved a complete remission, one achieved a partial response and two were non-responders." The survival range was five to 45 months, with only one patient dying from progressive neoplastic disease and none dying as a result of chemotherapy complications.
While NHL is the most common form of cancer found among American children, researchers in Uganda are documenting a dramatic rise of Kaposi's sarcoma (KS) in Ugandan children. Detection of the genome in children and the association of KS and HIV suggest that the causative virus has a nonsexual mode of transmission in Ugandan children, the researchers said.
Since January 1995, all children with a clinical and histological picture compatible with KS were recruited as cases and other children with cancers recruited as controls: 248 children in all with 65 cases and 183 controls. The children's biological mothers, when available, were recruited as "case mothers," or "control mothers." All were counseled and tested for HIV and a demographic and lifestyle questionnaire administered.
"HIV infection in the child and the mother are the strongest risk factors for childhood KS," said S.M. Mbulaiteye, MD, of the Uganda Cancer Institute in Kampala, who presented his study here. "KS diagnosis has apparently increased in HIV-positive as well as HIV-negative children in Uganda. Our analysis suggests that the virus is ubiquitous in Uganda and may be acquired early in life."
Although not every child with AIDS and cancer will be a candidate for intensive therapy, Mueller said if the child is in reasonable health, nihilism is not warranted. More importantly, if the treatment is initiated, it should always be with an intent to "cure" the child of the malignancy even though the prospect for an AIDS cure is currently not possible.
"The problem those of us in the pediatric AIDS field are confronting is 'why should research be done in the field of HIV-related malignancies when the number of those suffering is so small?'" Mueller said. "However, with longer survival of HIV-infected patients, we might see an increase in the incidence of cancer in the future."
For more information:
- Mbulaiteye SM. Risk factors for childhood Kaposi's sarcoma in Uganda: A case control study. Presented at the First National AIDS Malignancy Conference. April 28-30. Bethesda, Md.
- Mueller B. Malignancies in HIV-infected children. Presented at the First National AIDS Malignancy Conference. April 28-30. Bethesda, Md.
- Mueller B, Pizzo PA. Malignancies in pediatric AIDS. Pediatrics. 1996. 8:45-49.
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