[Prognosis, treatment completion, and complications in nonresponders in the study AML-BFM87].
BACKGROUND
Nonresponders (NR) are patients (pts.) with no or insufficient response to initial treatment, which may be caused by either initial risk factors or poor therapy realization. In study AML-BFM 87, 49 NR of 307 patients (16%) did not achieve remission until the end of intensive chemotherapy and were analysed to assess the specific contribution of prognostic factors, therapy realization and complications of therapy. THERAPY AND METHODS: Therapy started with an 8-day induction therapy followed by a 6-week consolidation and two 5-day intensification blocks with high-dose cytosine-arabinoside and VP-16. Maintenance therapy was given for a total duration of 1.5 years. To evaluate the impact of treatment intensity in NR, we compared the dose compliance (DC = dose given/intended dose), the dose intensity (DI = dose per time given), the treatment results, and toxicity of the individual therapy phases in responders (CR) and NR.


RESULTS
In 19 of 49 NR therapy was stopped before starting intensification blocks. Twenty-six NR received at least one block of intensification, and seven patients between three and six intensification blocks. Six children entered maintenance therapy. Twelve patients received a bone marrow transplant (9 allogeneic, 3 autologous). Six (5 after bone marrow transplantation) of 49 NR are still alive for 64 to 108 months. In nearly all patients induction therapy could be applied according to protocol (mean DC: 98%, range 85%-100%), whereas therapy realization was more difficult in the 2nd phase of therapy (mean DC: 92%, range 12%-113%). Deviations from the protocol in the treatment blocks (changes of dose and/or schedule) were mainly attributable to persistence of blasts (n = 33) and septic complications (n = 24). The mean relative DI of 1.01 was according to protocol. Bleeding and infectious complications in the individual therapy phases varied from 7% to 61%. NR compared to CR patients suffered significantly more often from bleeding during the first and second part of consolidation and from infections during the second part of consolidation. Withdrawal from protocol in NR was mainly due to persistence of blasts (n = 16), followed by bone marrow transplantation or other therapies (n = 13), and sepsis (n = 11).


CONCLUSIONS
It is difficult to discriminate between nonresponse associated with blast persistence followed by complications and subsequent discontinuation of therapy and nonresponse due to insufficient therapy in patients with complications. Our analyses revealed that therapy with 2 intensifications according to protocol was feasible in 13 NR. Patients' condition permitting, therapy should not be stopped prematurely, in order to sustain the option of BMT after blast cell reduction.
Kallage
V
V
Klinik und Poliklinik für Kinderheilkunde, Pädiatrische Hämatologie und Onkologie, Münster.
Müller
J E
JE
Zimmermann
M
M
Beck
J D
JD
Ritter
J
J
Creutzig
U
U
D000208:Acute Disease; D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002648:Child; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D012074:Remission Induction; D016019:Survival Analysis; D017211:Treatment Failure
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003561:Cytarabine; D005047:Etoposide