Treatment of lymphoid malignancies in patients with ataxia-telangiectasia

Abstract

Background Patients with ataxia‐telangiectasia (A‐T) are at an increased risk for developing lymphoid malignancies, yet the appropriate therapy remains unknown. Radiation therapy at conventional doses results in destruction of normal tissue, which has suggested that full‐dose chemotherapy might result in unacceptable toxicity in A‐T patients with cancer. Procedure The medical records of 412 A‐T patients were reviewed to identify those patients who developed lymphoid malignancies and to analyze the type and duration of therapy, events during therapy, and off‐therapy follow‐up. Results Of 74 A‐T patients with lymphoid malignancies, 32 patients received chemotherapy. The 21 patients treated with standard chemotherapy had a significantly better median survival (9 months, range, 1–162+ months vs. 5 months, range, 0.5–28 months) (P= 0.03) and complete remission rate (76% vs. 9%) (P = 0.001) than the 11 treated with reduced dose chemotherapy. Three of the 21 full‐dose chemotherapy patients required dose reductions because of neutropenia. Seven of the 14 patients exposed to 1,200 mg/m2 or greater of cyclophosphamide developed hemorrhagic cystitis. All three patients exposed to bleomycin developed pulmonary disease which was fatal in two. Of the 16 standard‐dose chemotherapy patients who achieved a complete remission, two remain disease‐free, five have died of recurrent disease, and five died of pulmonary disorders and four of other causes while in remission. Conclusions Standard‐dose chemotherapy should be given to each A‐T patient with a lymphoid malignancy unless additional physical or emotional problems make it unlikely that the patient will benefit. Morbidity and mortality may be reduced by prophylaxis against hemorrhagic cystitis and early detection and treatment of pulmonary disorders. Med. Pediatr. Oncol. 31:491–497, 1998. © 1998 Wiley‐Liss, Inc.

Chemo- And Radiosensitivity Testing in a Patient With Ataxia Telangiectasia and Hodgkin Disease

“…AT cells were found to be slightly more sensitive to doxorubicin treatment in vitro and caused no substantial in vivo toxicity even when given at the maximal tolerable dose for non-AT patients. Although some malignancies and occasionally HD in AT patients can be cured, despite reductions in standard radiotherapy and/or chemotherapy [17, 19, 23± 25], the overall survival of AT patients with a malignancy is poor [20]. Based on our observations, we suggest treating AT patients as much as possible according to standard protocols by combining radiotherapy and chemotherapy and adjusting both to individual doses derived from in vitro radio-and chemosensitivity testing.…”

“…Based on the above-mentioned data, we think radiotherapy can and should be part of the treatment of Hodgkin disease in AT patients. [19] ABV/COPP(CVPP)# † 22 Secondary leukemia 1995 [19] ABV/COPP# NED 16C 1998 [20] RT † <7 ND 1998 [20] RT † <7 ND 1998 [20] ABVD## † 4 Pulmonary toxicity (nodules) 1998 [20] OPA/ChVPP † 17 ND 1998 [20] ABVD# † 3 Pulmonary toxicity (® brosis) 1998 [20] PE † 28 ND 2000 [29] OPPA † 16 Pneumonia OPPA/ABVD † 6 Pneumonia (CMV) This report RT 900 and OPA## † 6 Progressive disease, pneumonia…”

B-Cell Acute Lymphoblastic Leukemia in a Child With Ataxia Telangiectasia

“…Non-Hodgkin lymphoma was the most frequent, 48 (64%); followed by acute leukemia, 11 (15%); Hodgkin disease, 10 (13%); and CLL, 3 (4%). Occurrence of different solid tumors in association with lymphoid malignancies in A-T patients was also observed [4]. T-cell acute lymphoblastic leukemia is more frequent than B-cell ALL.…”

Treatment and management issues in ataxic diseases

“…The stress and immobilization that accompany surgical interventions may also lead to a functional decline that may not recover to the prior baseline. Patients with ataxia-telangiectasia and neoplasm should follow cancer treatment protocols that are minimally radiomimetic, due to increased radiation sensitivity in this disorder (Sandoval and Swift, 1998).…”