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Original Article
Original Article
Original Article
Original article
Table I. Main characteristics of the 41 patients included in the study Table 2. Protocols CVBA and CVA.
for recurrent ALCL.
CVBAa
Age at diagnosis (months) CCNU 100 mg/m2 p.o. Dl
Median Vinblastine 6 mg/m2 i.v. Dl, 15,22
Range 17-190 Bleomycin 20 mg/m2 i.v. Dl, 15,22
Sex Ara-C (replaces bleomycin when
Male 17 a total dose of 200 mg/m 2 of
Female 24 bleomycin is reached) 100 mg/m2 i.v. Dl-5
Immunophenotype CVAa
CD30 41 positive/41 tested CCNU 100 mg/m2 p.o. Dl
EMA 40 positive/40 tested Vinblastine 6 mg/m2 i.v. Dl,8, 15,22
ALK. 36 positive/39 tested Ara-C 100 mg/m2 i.v. Dl-5
T 23 positive/31 tested
Null 8 positive/31 tested ' Courses every six weeks for 12 months.
Stage at diagnosis according to St. Jude's
classification
I —II 6 Response assessment
III-IV 35
First-line treatment Complete remission (CR) was defined as the complete disappearance
COPAD 12 of all lesions for at least four weeks. Partial response (PR) was defined
HM89 8 as a regression of more than 50% of all the tumor sites without the
HM91 21 appearance of new lesions. Progressive disease (PD) was defined as an
Time to relapse increase in measurable disease or by the appearance of any new lesion.
Median delay (months post diagnosis) 10 months (1.6-58)
COPAD 6 months (1.6-58)
HM 89 and 91 10 months (7-55) Statistical analysis
Relapse on treatment 9 patients
Relapse within 12 months 24 patients Overall survival rates were estimated using the Kaplan-Meier method
Site of relapse [25] from the date of the first relapse to death or to the date of the last
Lymph node 38 observation for the patients who were still alive. Disease-free survival
Skin 9 rates (DFS) were estimated from the date of the first relapse to the time
Bone marrow 6 of documented failure (date of the relapse for patients who did not
Lung 5 achieve a second CR, the time of the second relapse or the time of
CNS 1 death for the others) or to the date of the last observation for those in
Other (spleen, kidney, pericardium, soft second CR. Follow-up data were updated on 1 March 1998. Statistical
tissue) differences in DFS were tested by the two-tailed log-rank test. As the
Type of relapse number of patients included in this study is rather small, only four
Local 10 factors were tested in univariate analysis: recurrence occurring during
New localisations 14 or after treatment, time to relapse less or more than 12 months, first-
Local and new localisations 17 line treatment and ABMT in CR2.
First-line treatment
Results
The first group of patients were treated with a 12-18-month chemo-
therapy regimen combining vincristine, doxorubicin, cyclophospha- First relapses
mide, prednisone and intrathecal methotrexate [21]. For the second
and third groups of patients, the same drugs were combined with high-
Overall, 36 of 41 patients achieved a CR. One patient is
dose methotrexate and etoposide for the HM89 protocol and with
high-dose methotrexate, etoposide, bleomycin and vinblastine in the not evaluable for response to second-line chemotherapy
HM91 protocol [22]. The duration of the treatment was seven to eight since he underwent resection of the entire tumor mass
months for these latter groups. No patient had high-dose chemo- for the diagnosis of the relapse before the beginning of
therapy with autologous bone marrow transplantation at first complete chemotherapy. Among the 40 patients who are evaluable
remission (CR) except for one in the HM91 series whose disease
progressed during first-line treatment
for response, 35 (88%) achieved a CR following various
chemotherapy regimens: 25 with CVA or CVBA, 2 with
high-dose ara-C VP16 according to the CYVE protocol
Second-line treatment [26], 3 with vinblastine and 5 with other regimens. Five
patients did not achieve CR and died of progressive
The second-line chemotherapy protocols were somewhat heterogene-
ous since the choice of the treatment for relapse was left to each center.
disease seven to twenty-two months after the first re-
However, in the first two series of patients, the protocol suggested for lapse (median 16 months). The CR rate did not vary
relapses was the CVBA, combination which had previously been tested significantly according to the first-line chemotherapy
for relapsed lymphoma in the Pediatrics department at Institut previously used. It was 92% (11 of 12) for patients
Gustave Roussy (Table 2). The treatment suggested for relapses for the
HM91 series, was CVA (Table 2). Intensification with a high-dose
treated with COPAD, 88% (7 of 8) for patients treated
regimen and autologous bone marrow (or peripheral stem cell) trans- with HM89 and 90% (17 of 20) for patients treated with
plantation (ABMT) was strongly recommended for patients in second HM91 (P = 0.95). After the second CR, 15 patients
remission (CR2) in this third series. underwent ABMT after 2-4 months of conventional
55
60%-
On/off treatment
Relapse on treatment 9 5 44(19-73) 0.23a
\ Relapse off treatment 32 16 43(25-62)
40%- 1 Time to relapse
Early relapse (< 12 m) 24 16 28(14-50) 0.01b
Late relapse (> 12 m) 17 5 68(16-78)
Overall survival
20%- First-line treatment
— Disease-free survival COPAD 12 5 58(32-81) 0.02c
HM89orHM91 29 16 30(14-52)
0%- 1 1 1 1 1- 1 1 1 1 1 1 1 ABMTinCR2
9 10 11 12
Years after first relapse Yes 15 6 45(20-73) 0.55d
No 21 10 52(31-73)
At risk
a
41 31 22 20 19 16 13 12 11 6 Adjusted on first-line treatment.
b
Adjusted on first-line treatment and ABMT.
-41 23 13 12 11 10 9 c
Adjusted on the time to relapse ( > or < 12 months).
d
Figure 2. Overall and disease-free survival of 41 children with relapsed Ajusted on the time to relapse (> or < 12 months). For this analysis,
ALCL. only patients who achieved a CR2 were taken into account.
UU70 "
especially the indications for ABMT, have been subject
to considerable changes according to the period.
80%-
h no BMT in CR2, 1 = 21
maintained the CR over time. In the present study, the first-line treatment and of the optimal treatment for
three-year DFS of patients treated with ABMT in CR relapses will only be possible through large international
is rather good (45%, 20%-73%). In univariate analysis, randomized studies.
it was not, however, statistically different from the DFS
of patients treated without ABMT in second CR (52%,
31%—73%). Comparison of the outcome of the patients Acknowledgements
treated with or without ABMT should, however, be inter-
preted with caution because the indications for BMT This work was supported by the ARC (Association pour
varied according to the treatment period. Patients who la Recherche contre le Cancer).
did not undergo BMT in second CR were mostly those Acknowledgments to L. Saint Ange for editing the
treated before 1991 with COPAD or the HM89 protocol manuscript.
asfirst-linetreatment whereas almost all the patients who
relapsed after HM91 chemotherapy underwent ABMT
in second CR. The long-lasting CR obtained with con-
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