VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

esponses with persistent nodular disease.
Sixteen of 20 (80%) limited stage patients received chest radiotherapy; three
before and 13 after high dose therapy. Toxicity precluded chest radiotherapy in
four patients: congestive heart failure, interstitial pneumonitis, persistent
thrombocytopenia and early infectious death in one patient each. The median
doses to the extended (primary lesion, hilum, mediastinum and bilateral
supraclavicular areas) and involved fields were 40.0 (16-45) Gy and 50 (16-59.4)
Gy, respectively. Four extensive stage patients received chest with or without
additional involved field sites. The other patients had disease too widespread to
administer radiotherapy. Prophylactic cranial irradiation (PCI) (median dose 30
Gy in 2 Gy fractions) was given to 16 limited and four extensive stage patients.
One patient had therapeutic cranial radiation prior to high dose therapy.
Toxicity to the high dose therapy is summarized in Table 2. Two patients
died (7%) of Candida sepsis. Aside from the expected fever during neutropenia,
interstitial pneumonitis was the principal morbidity. The median decline in the
% predicted FEV1 and FVC was 4-6%, but DLCO decreased by 22%. Seven patients
(23%) developed dyspnea, non-productive cough, intermittent fever, and
a chest x-ray pattern compatible with interstitial pneumonitis within three
months of high dose chemotherapy. All responded promptly to two weeks of 1
mg/kg prednisone followed by a gradual taper over three to four weeks. Three
had recurrent symptoms (one following an abbreviated course of chest radiotherapy)
and required prolonged steroid treatment with slow taper over 2-3
months. One patient each developed Pneumocystis carinii and cerebral
toxoplasmosis following steroid therapy.
Four patients developed severe but reversible congestive heart failure. Reversible
elevations in creatinine were observed in sixteen patients, appearing
immediately after completion of chemotherapy administration in four. The remainder
occurred after prolonged aminoglycoside and amphotericin B exposure.
One patient developed reversible hemolytic uremic syndrome seven
months after high dose therapy. The single patient who had cranial radiotherapy
six weeks prior to high dose therapy developed an acute, prolonged (2
months), but eventually reversible encephalopathy, a toxicity that had not been
observed in any other patients.
Response to High Dose Chemotherapy: Fourteen patients were not évaluable for
response to high dose chemotherapy (nine were in complete response, two had
persistent but unchanged radiologic abnormalities and were found to be free of
disease at subsequent surgical staging, one had bone scan findings with sclerosis
on plain radiograph, and two died of toxicity). Of the 16 patients évaluable for
response, 11 achieved complete response after high dose chemotherapy for an
overall partial to complete response conversion rate of 69%.
Event-free survival and relapse (Table 3; Figure 2): The median event-free survival
from high dose therapy for all patients, limited stage, and extensive stage
patients was 11,16, and 10 months, respectively. The 2-year event-free survival
for the subset of limited stage patients in or near complete response prior to
high-dose chemotherapy was 60%. Of the seventeen patients who relapsed with
SCLC, 15 occurred within the first year after high dose therapy with a median
time from relapse to death of 5 (2-27) months. Relapse was most commonly in
sites of prior involvement (summarized in Table 3). One patient, originally diag-
164 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION