TY - JOUR
T1 - Unexpected high incidence of severe toxicities associated with alpha interferon, low-dose cytosine arabinoside and all-trans retinoic acid in patients with chronic myelogenous leukemia
AU - Sacchi, Stefano
AU - Kantarjian, Hagop M.
AU - Freireich, Emil J.
AU - O' Brien, Susan
AU - Cortes, Jorge
AU - Rios, Mary Beth
AU - Kornblau, Steve
AU - Giles, Francis J.
AU - Koller, Charles
AU - Gajewski, James
AU - Talpaz, Moshe
PY - 1999/1/1
Y1 - 1999/1/1
N2 - Preclinical data have shown that all-trans retinoic acid (ATRA) with interferon-alpha (IFN-α) can exert significant suppressive effects on Philadelphia-chromosome (Ph)-positive cells. The aim of this study combining IFN-α, low-dose cytosine arabinoside (ara-C) and ATRA was to increase the proportion of patients achieving a major cytogenetic response, in comparison with a group of 140 patients previously treated with IFN-α plus low-dose ara-C. Forty three patients with Ph-positive CML in early chronic phase were treated with IFN-α 5 MU/m2 sc daily, low-dose ara-C 10 mg sc daily and ATRA 45 mg/m2 orally daily, for 7 consecutive days every other week. Overall, 76% of patients achieved a complete hematologic response (CHR). A cytogenetic response was in observed 59% (major in 38% and complete in 17%). Compared with patients treated with IFN-α and low-dose ara-C, those receiving additional ATRA had a lower CHR rate (p. 014), but other response rates were similar. Severe toxicities were common with the triple regimen (64%), mostly related to ATRA therapy. Two patients experienced pseudotumor cerebri; two patients had leukocytosis during the week on ATRA treatment, decreasing during the week off (one suffered a severe asthma-like reaction followed by pulmonary edema, resembling ATRA syndrome). Six patients had other unusual side-effects: aseptic necrosis of the hip (1 patient), ataxic syndrome (1 patient), paranoid syndrome (2 patients), syncopal episodes (1 patient), pure red cell aplasia (1 patient). In conclusion the results of IFN-α and low-dose ara-C combined with ATRA in patients with early CML-chronic phase were disappointing, due to excessive toxicity. Whether different ATRA dose schedules may result in fewer side-effects and improve hematologic and cytogenetic response remains to be determined.
AB - Preclinical data have shown that all-trans retinoic acid (ATRA) with interferon-alpha (IFN-α) can exert significant suppressive effects on Philadelphia-chromosome (Ph)-positive cells. The aim of this study combining IFN-α, low-dose cytosine arabinoside (ara-C) and ATRA was to increase the proportion of patients achieving a major cytogenetic response, in comparison with a group of 140 patients previously treated with IFN-α plus low-dose ara-C. Forty three patients with Ph-positive CML in early chronic phase were treated with IFN-α 5 MU/m2 sc daily, low-dose ara-C 10 mg sc daily and ATRA 45 mg/m2 orally daily, for 7 consecutive days every other week. Overall, 76% of patients achieved a complete hematologic response (CHR). A cytogenetic response was in observed 59% (major in 38% and complete in 17%). Compared with patients treated with IFN-α and low-dose ara-C, those receiving additional ATRA had a lower CHR rate (p. 014), but other response rates were similar. Severe toxicities were common with the triple regimen (64%), mostly related to ATRA therapy. Two patients experienced pseudotumor cerebri; two patients had leukocytosis during the week on ATRA treatment, decreasing during the week off (one suffered a severe asthma-like reaction followed by pulmonary edema, resembling ATRA syndrome). Six patients had other unusual side-effects: aseptic necrosis of the hip (1 patient), ataxic syndrome (1 patient), paranoid syndrome (2 patients), syncopal episodes (1 patient), pure red cell aplasia (1 patient). In conclusion the results of IFN-α and low-dose ara-C combined with ATRA in patients with early CML-chronic phase were disappointing, due to excessive toxicity. Whether different ATRA dose schedules may result in fewer side-effects and improve hematologic and cytogenetic response remains to be determined.
KW - ATRA
KW - All-trans retinoic acid
KW - Alpha interferon
KW - CML
KW - Chronic myelogenous leukemia
KW - Low-dose ara-C
KW - Severe toxicity
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U2 - 10.1080/10428199909169612
DO - 10.1080/10428199909169612
M3 - Article
C2 - 10609785
AN - SCOPUS:0033400136
SN - 1042-8194
VL - 35
SP - 483
EP - 489
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 5-6
ER -