Double autotransplant in refractory lymphomas: the tmj/ice stupy
Magnetic Resonance Imaging
To confirm indications that patients (pts) with either Hodgkin's (HD) or nonHodgkin's (NHL) lymphoma refractory to previous standard-dose treatment can achieve relatively good response rates and survival with a double autotransplant, we offered a single transplant to pts in responsive relapse, and two consecutive transplants to those with disease refractory either ab initie or during the last relapse. Pts were required to have acceptable renal, myocardial and pulmonary function and not to have been previously transplanted. The dose-intensive conditioning regimen for the first (or single) transplant was TMJ (thiotepa, mitoxantrone and carboplatin) and, for the second, ICE (ifosfamrde, carboplatin and etoposide}. The second treatment was given to pts with refractory disease in the absence of progression or excessive non-hematologic toxicity. Peripheral blood with or without bone marrow was used lor autotransplant. A total of 68 pts have been entered from 9/94 to 1/97. Of the 25 with HD (15 women and 10 men, aged 22-61, median 33), 9 had a sensitive relapse, 4 refractory relapse and 12 primary refractory disease. All pts with refractory disease received 2 courses. 3/9 with sensitive and 6/16 pts with refractory disease (4 of whom had no response to the first course) achieved a CR. There were 3/25 peritransplant deaths, 2 in pts in sensitive refapse and 1, in the 2nd transplant, in a pt with refractory disease. Median follow-up is 20 months and the actuarial survival median has not been reached for either sensitive or refractory patients. No difference in survival curves can be evidenced according to prior response status, sex, age group, performance status, number of prior regimens, previous radiotherapy, while survival is significantly shorter in patients initially presenting in stage II disease. At 12-24 months, 4/12 refractory HD pts remain continuously with no evidence of disease (NED). Of the 43 pts with NHL, 7 had low grade, 23 intermediate and 13 high grade malignancy. The 26 men and 17 women were aged 25-70 with a median of 55. 22 pts had sensitive relapse while 10 were in refractory relapse and 11 had primary refractory disease. 12/21 refractory pts received 2 transplants. There were 4/43 peritransplant deaths, and CR was maintained or achieved in 11 /22 pts with sensitive and 4/21 wrîh refractory disease (difference significant). Median foltow-up is 15 months and the 2-year actuarial median is 50%. Median survival has not been reached for pts with either sensitive relapse or primary refractory disease, whose curves are superposable, while the median for pts wtth refractory relapse is 8 months only. No other initial characteristics correlate with survival, except initial stage II which is an adverse factor. Progression-free survival is worse for pts with more than 2 prior treatment regimens. At 12-24 months, 5/16 refractory NHL pts remain continuously NED. New strategies can impact outcome for pts with refractory lymphomas. This study confirms that refractoriness to past standard-dose treatment does not necessarily justify withholding autotransplant from pts with HD or NHL.