Observational Studies of IFN- Only in the Treatment of CML
| Authors, Year . | No.Patients . | Population Description . | Initial Dose rIFN-α (MU/M2/d)* . | Med f-u (mo) . | Outcomes . | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Hematologic Response† . | Cytogenetic Response‡ . | Survival . | ||||||||
| CHR % . | PHR % . | CCyR % . | PCyR % . | 5-yr % . | Med (mo) . | |||||
| Ozer et al,16 1993 | 107 | CP-Ph+, med age = 44, mo from dx NR, CALGB Score 0-3, life expectancy >12 mo, 56% with splenomegaly, none with prior treatment | 5 | 64 | 22 | 20 | 13 | 16 | 52 | 66 |
| Thaler et al,55 1993 | 80 | CP-Ph+, med age = 49, mo from dx and clinical characteristics NR, 24% with prior treatment | 3.5 | 12 | 36 | 33 | 5 | 5 | NR | NR |
| Alimena et al,19 1988 | 73 | CP-Ph+, med age = 40-43; 57% with prior treatment | 2 or 5 | 14 | 49 | 19 | med, Ph+ cells = 65% | NR | NR | |
| Montastruc et al,21 1995 | 52 | CP-Ph+, med age = 52, ≤6 mo (med) from dx, 46% with splenomegaly, 27% with prior treatment | 5 | 30 | 81 | 17 | 38 | 6 | NR | NR |
| Fernandez-Ranada et al,17 1993 | 51 | CP-Ph+, med age = 43, 2 mo (med) from dx, Karnofsky ≥80%, 100% with prior treatment | 5 | 7 | 53 | 22 | 6 | 2 | NA | — |
| Talpaz et al,141987 | 51 | CP-Ph+, med age = 42, 90% <6 mo from dx, <30% “blasts,” 71% with splenomegaly, no extramedullary disease, some with prior treatment | 3-9 | 37 | 71 | 10 | NR | 16 | med survival not reached; 78% alive at 37 mo, 3-yr survival = 76% | |
| Niederle et al,47 1993 | 48 | CP-Ph+, med age = 36, 13 mo (med) from dx, 76% with prior treatment | 4 | NR | 46 | 27 | 0 | 2 | NR | NR |
| Schofield et al,48 1994 | 41 | CP-Ph+, med age = 38, 7 mo (med) from dx, 70% with splenomegaly, some with prior treatment | 2 | 52 | 61 | 20 | 7 | 12 | 54 | 84 |
| Freund et al,49 1989 | 27 | CP-Ph+, med age = 47, 0-81 mo from dx, severe renal, hepatic, cardiac, cerebral ds or pregnancy excluded, 63% with prior treatment | 5 (TIW) | 30 | 22 | 37 | 0 | 0 | NR | NR |
| Talpaz et al,13 1986 | 17 | CP-Ph+, med age = 44, 4 mo (med) from dx, not treated for 2 wk before study, 76% with prior treatment | 5 | NR | 76 | 6 | 35 | NR | NR | NR |
| Werter et al,50 1988 | 14 | CP-Ph+, med age = 43, mo from dx NR, 50% with prior treatment | 5 | — | 7 | 50 | NR | NR | NR | NR |
| Hermann et al,51 1990 | 11 | CP-Ph+, med age = 45, mo from dx NR, Karnofsky Score >50%, life expectancy >3 mo, normal hepatic, renal, coag fxn, >4 wk from previous rx, 100% with prior treatment | 5 | 6-30 | 36 | 9 | 9 | 9 | NR | NR |
| Authors, Year . | No.Patients . | Population Description . | Initial Dose rIFN-α (MU/M2/d)* . | Med f-u (mo) . | Outcomes . | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Hematologic Response† . | Cytogenetic Response‡ . | Survival . | ||||||||
| CHR % . | PHR % . | CCyR % . | PCyR % . | 5-yr % . | Med (mo) . | |||||
| Ozer et al,16 1993 | 107 | CP-Ph+, med age = 44, mo from dx NR, CALGB Score 0-3, life expectancy >12 mo, 56% with splenomegaly, none with prior treatment | 5 | 64 | 22 | 20 | 13 | 16 | 52 | 66 |
| Thaler et al,55 1993 | 80 | CP-Ph+, med age = 49, mo from dx and clinical characteristics NR, 24% with prior treatment | 3.5 | 12 | 36 | 33 | 5 | 5 | NR | NR |
| Alimena et al,19 1988 | 73 | CP-Ph+, med age = 40-43; 57% with prior treatment | 2 or 5 | 14 | 49 | 19 | med, Ph+ cells = 65% | NR | NR | |
| Montastruc et al,21 1995 | 52 | CP-Ph+, med age = 52, ≤6 mo (med) from dx, 46% with splenomegaly, 27% with prior treatment | 5 | 30 | 81 | 17 | 38 | 6 | NR | NR |
| Fernandez-Ranada et al,17 1993 | 51 | CP-Ph+, med age = 43, 2 mo (med) from dx, Karnofsky ≥80%, 100% with prior treatment | 5 | 7 | 53 | 22 | 6 | 2 | NA | — |
| Talpaz et al,141987 | 51 | CP-Ph+, med age = 42, 90% <6 mo from dx, <30% “blasts,” 71% with splenomegaly, no extramedullary disease, some with prior treatment | 3-9 | 37 | 71 | 10 | NR | 16 | med survival not reached; 78% alive at 37 mo, 3-yr survival = 76% | |
| Niederle et al,47 1993 | 48 | CP-Ph+, med age = 36, 13 mo (med) from dx, 76% with prior treatment | 4 | NR | 46 | 27 | 0 | 2 | NR | NR |
| Schofield et al,48 1994 | 41 | CP-Ph+, med age = 38, 7 mo (med) from dx, 70% with splenomegaly, some with prior treatment | 2 | 52 | 61 | 20 | 7 | 12 | 54 | 84 |
| Freund et al,49 1989 | 27 | CP-Ph+, med age = 47, 0-81 mo from dx, severe renal, hepatic, cardiac, cerebral ds or pregnancy excluded, 63% with prior treatment | 5 (TIW) | 30 | 22 | 37 | 0 | 0 | NR | NR |
| Talpaz et al,13 1986 | 17 | CP-Ph+, med age = 44, 4 mo (med) from dx, not treated for 2 wk before study, 76% with prior treatment | 5 | NR | 76 | 6 | 35 | NR | NR | NR |
| Werter et al,50 1988 | 14 | CP-Ph+, med age = 43, mo from dx NR, 50% with prior treatment | 5 | — | 7 | 50 | NR | NR | NR | NR |
| Hermann et al,51 1990 | 11 | CP-Ph+, med age = 45, mo from dx NR, Karnofsky Score >50%, life expectancy >3 mo, normal hepatic, renal, coag fxn, >4 wk from previous rx, 100% with prior treatment | 5 | 6-30 | 36 | 9 | 9 | 9 | NR | NR |
Abbreviations: CCyR, complete cytogenetic response; PCyR, partial cytogenetic response; CHR, complete hematologic response; CP, chronic phase; NA, not applicable; NR, not reported; PHR, partial hematologic response; TIW, 3 times per week; ds, disease; dx, diagnosis; f-u, follow-up period (mo); fxn, functions; med, median; med age, in years; rx, treatment; BMT, bone marrow transplantation.
Protocols highly variable across studies. Dosage generally increased to highest tolerable dose or specified maximum (eg, 5, 7, or 10 MU/d), continued for variable periods (1-40 months, depending on study), and reduced or discontinued for remission, no response, disease progression, toxicity, or crossover to BMT. Induction protocols specified only in selected studies.
Generally based on M.D. Anderson criteria, but details of definition vary across studies. M.D. Anderson criteria: CHR = WBC count, platelet count, and differential all normal and disappearance of symptoms/signs; PHR = decrease in WBC count to <50% of pretreatment level and <20,000/μL or normalization of WBC count with persistent splenomegaly or immature cells in the peripheral blood.
With exception of Alimena et al and Ozer et al, defined on the basis of M.D. Anderson criteria and the percentage of Ph+ metaphases on most favorable karyotype. M.D. Anderson Criteria: CCyR = 0% Ph+ metaphases; PCyR = 5% to 34% Ph+. Denominator used for calculating response rates is original sample size. Most investigators report higher rates by excluding 8% to 51% of the sample from the denominator as “nonevaluable” patients who had poor hematologic response, short follow-up, or unavailability for testing.