Predicting complete cytogenetic response in chronic myelogenous leukemia patients treated with recombinant interferon alpha [letter; comment]

The authors treated a total of 82 patients with Ph′-positive chronic myelogenous leukemia (CML) with recombinant interferon alpha-2b (IFN alpha-2b). Sixty-five patients in chronic phase (CP), 28 of whom were untreated and 37 pretreated, and nine patients in accelerated phase (AP), were started on IFN three times a week. Patients in CP were randomized to receive 2 or 5 X 10(6) IU/m2, while patients in AP were all given the dose of 5 X 10(6) IU/m2, in addition to concomitant chemotherapy. Patients in CP who were unresponsive to the lower dose were crossed to the higher dose. Of 63 evaluable patients in CP, 43 (68%) responded, 29 (46%) achieved complete hematologic response (CHR), and 14 (22%) achieved partial hematologic response (PHR). The response rate appeared to be significantly influenced by the IFN dose in pretreated patients. Of the nine patients in AP, two attained PHR and one CHR. More recently, eight previously untreated CP cases were submitted to daily IFN administration at doses from 2 to 5 X 10(6) IU/m2. This daily schedule was also applied to patients who had obtained, with the intermittent treatment, a PHR persisting unmodified for six months (nine patients) or an unstable CHR (five patients). Seven of the eight previously untreated patients, and five of the nine PHR patients crossed to daily IFN reached CHR. In the total series of previously untreated patients, the response rate proved to be significantly influenced by the initial risk status. Cytogenetic improvement was seen in 37 of 53 responders (70%) treated for more than 3 months, the median of Ph′-positive cells declining from 100% to 65% (range 0% to 95%). Complete suppression of Ph′ chromosome was observed in one case. The cytogenetic response was persistent for over 6 months in 21 patients, but the lowest value of Ph′ positivity was usually unstable. At a median follow-up of 56 weeks, 23 of 36 (64%) CHR patients remain in continued disease control with IFN. A blastic transformation (BT) occurred in seven of 21 unresponsive patients and in one of the 36 CHR patients. The authors' data confirm that IFN alpha- 2b, especially at daily doses, is effective in inducing clinical and cytogenetic response in a good proportion of patients with CML in the benign phase. Longer follow-ups will define the exact influence of this agent on the natural course of the disease.

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Interferon alpha-2b as therapy for Ph'-positive chronic myelogenous leukemia: a study of 82 patients treated with intermittent or daily administration

Blood ◽

10.1182/blood.v72.2.642.642 ◽

1988 ◽

Vol 72 (2) ◽

pp. 642-647 ◽

Cited By ~ 134

Author(s):

G Alimena ◽

E Morra ◽

M Lazzarino ◽

AM Liberati ◽

E Montefusco ◽

...

Keyword(s):

Chronic Myelogenous Leukemia ◽

Interferon Alpha ◽

Response Rate ◽

Cytogenetic Response ◽

Myelogenous Leukemia ◽

Complete Suppression ◽

Recombinant Interferon ◽

Hematologic Response ◽

Interferon Alpha 2B ◽

Ifn Alpha

Abstract The authors treated a total of 82 patients with Ph′-positive chronic myelogenous leukemia (CML) with recombinant interferon alpha-2b (IFN alpha-2b). Sixty-five patients in chronic phase (CP), 28 of whom were untreated and 37 pretreated, and nine patients in accelerated phase (AP), were started on IFN three times a week. Patients in CP were randomized to receive 2 or 5 X 10(6) IU/m2, while patients in AP were all given the dose of 5 X 10(6) IU/m2, in addition to concomitant chemotherapy. Patients in CP who were unresponsive to the lower dose were crossed to the higher dose. Of 63 evaluable patients in CP, 43 (68%) responded, 29 (46%) achieved complete hematologic response (CHR), and 14 (22%) achieved partial hematologic response (PHR). The response rate appeared to be significantly influenced by the IFN dose in pretreated patients. Of the nine patients in AP, two attained PHR and one CHR. More recently, eight previously untreated CP cases were submitted to daily IFN administration at doses from 2 to 5 X 10(6) IU/m2. This daily schedule was also applied to patients who had obtained, with the intermittent treatment, a PHR persisting unmodified for six months (nine patients) or an unstable CHR (five patients). Seven of the eight previously untreated patients, and five of the nine PHR patients crossed to daily IFN reached CHR. In the total series of previously untreated patients, the response rate proved to be significantly influenced by the initial risk status. Cytogenetic improvement was seen in 37 of 53 responders (70%) treated for more than 3 months, the median of Ph′-positive cells declining from 100% to 65% (range 0% to 95%). Complete suppression of Ph′ chromosome was observed in one case. The cytogenetic response was persistent for over 6 months in 21 patients, but the lowest value of Ph′ positivity was usually unstable. At a median follow-up of 56 weeks, 23 of 36 (64%) CHR patients remain in continued disease control with IFN. A blastic transformation (BT) occurred in seven of 21 unresponsive patients and in one of the 36 CHR patients. The authors' data confirm that IFN alpha- 2b, especially at daily doses, is effective in inducing clinical and cytogenetic response in a good proportion of patients with CML in the benign phase. Longer follow-ups will define the exact influence of this agent on the natural course of the disease.

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Effect of Recombinant Interferon Alpha-2 on the Growth of Hematopoetic Progenitor Cells in Chronic Myelogenous Leukemia and Its Relationship to the Clinical Efficacy

Chronic Myelocytic Leukemia and Interferon ◽

10.1007/978-3-642-73526-4_4 ◽

1988 ◽

pp. 34-41 ◽

Cited By ~ 3

Author(s):

D. Geissler ◽

W. Aulitzky ◽

H. Tilg ◽

I. Von Lüttichau ◽

G. Konwalinka ◽

...

Keyword(s):

Progenitor Cells ◽

Chronic Myelogenous Leukemia ◽

Interferon Alpha ◽

Clinical Efficacy ◽

Myelogenous Leukemia ◽

Recombinant Interferon ◽

Recombinant Interferon Alpha

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A randomized trial comparing interferon-alpha with busulfan for newly diagnosed chronic myelogenous leukemia in chronic phase

Blood ◽

10.1182/blood.v86.3.906.906 ◽

1995 ◽

Vol 86 (3) ◽

pp. 906-916 ◽

Cited By ~ 140

Author(s):

K Ohnishi ◽

R Ohno ◽

M Tomonaga ◽

N Kamada ◽

K Onozawa ◽

...

Keyword(s):

Survival Rate ◽

Chronic Myelogenous Leukemia ◽

Interferon Alpha ◽

Philadelphia Chromosome ◽

Chronic Phase ◽

Cytogenetic Response ◽

Myelogenous Leukemia ◽

Newly Diagnosed ◽

Ifn Alpha ◽

Significant Difference

Abstract A multicenter randomized study was conducted to compare the effect of interferon-alpha (IFN-alpha) with that of busulfan in newly diagnosed patients with chronic myelogenous leukemia (CML) in chronic phase. From October 1988 to October 1991, 170 patients were randomized to receive either IFN-alpha or busulfan. Of 159 eligible patients, 31 (38.8%) of 80 patients in the IFN-alpha group and 43 (54.4%) of 79 patients in the busulfan group achieved complete hematologic remission, and 38.8% in the IFN-alpha group and 43.0% in the busulfan group achieved partial hematologic remission. A complete cytogenetic response was induced in seven (8.8%) of 80 patients treated with IFN-alpha and two (2.5%) of 79 patients treated with busulfan, and a partial cytogenetic response was 7.5% (6/80) and 2.5% (2/79), respectively. The difference in major (complete and partial) cytogenetic response between the two groups was significant (P = .046). At a median follow-up of 50 months, the predicted 5-year survival rate was 54% in the IFN-alpha group and 32% in the busulfan group (P = .0290), and the predicted 5-year rate of remaining in chronic phase was 41% in the IFN-alpha group and 29% in the busulfan group (P = .1165). As compared with the patients with no cytogenetic response, the patients with any cytogenetic response (complete, partial or minor) after the IFN-alpha or busulfan treatment were significantly superior in the duration of chronic phase (IFN-alpha group; P = .0017, busulfan group; P = .0010) even after correction for the time to response using the landmark analysis. However, there was no significant difference in survival rate in the IFN-alpha group (P = .1065). There was no significant difference in survival rate (P = .3923) and the duration of chronic phase (P = .6258) between the IFN- alpha and the busulfan group in the patients with a cytogenetic response (complete, partial or minor). These results demonstrate that IFN-alpha treatment produces a significantly superior cytogenetic response and survival rate as compared with the busulfan treatment, and unexpectedly, that busulfan can also eliminate Philadelphia chromosome positive clone in a few patients who showed prolonged survival rate and duration of chronic phase.

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GM-CSF can improve the cytogenetic response obtained with interferon-alpha therapy in patients with chronic myelogenous leukemia

Leukemia ◽

10.1038/sj.leu.2401033 ◽

1998 ◽

Vol 12 (6) ◽

pp. 860-864 ◽

Cited By ~ 30

Author(s):

J Cortes ◽

H Kantarjian ◽

S O’Brien ◽

R Kurzrock ◽

M Keating ◽

...

Keyword(s):

Chronic Myelogenous Leukemia ◽

Interferon Alpha ◽

Cytogenetic Response ◽

Myelogenous Leukemia ◽

Gm Csf ◽

Interferon Alpha Therapy ◽

Alpha Therapy

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Imatinib as Front-Line Treatment in Chronic Myelogenous Leukemia: How Important is the Achievement of Complete Cytogenetic Response after 3 Months?

Blood ◽

10.1182/blood.v114.22.4271.4271 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4271-4271

Author(s):

Roberto Latagliata ◽

Massimo Breccia ◽

Ida Carmosino ◽

Federico Vozella ◽

Paola Volpicelli ◽

...

Keyword(s):

Chronic Myelogenous Leukemia ◽

Risk Score ◽

Cytogenetic Response ◽

Myelogenous Leukemia ◽

Imatinib Treatment ◽

Front Line ◽

Prognostic Role ◽

Complete Cytogenetic Response ◽

Pre Treatment

Abstract Abstract 4271 The achievement of Complete Cytogenetic Response (CCyR) (Ph+ cells 0%) with Imatinib treatment still remains the most important objective in Chronic Myelogenous Leukemia (CML) patients. According to The European Leukemia NET guidelines, CCyR should be achieved within the 12th month of treatment while at 3 months of treatment the goal should be complete haematological response. To address the prognostic role of the early achievement of CCyR, we revised 108 chronic phase CML patients [M/F 57/51, median age 54.9 years, interquartile range (IR) 40.8 – 68.1] treated with front-line Imatinib at our Institution from June 2002 to June 2008 who had evaluable karyotype after 3 months of treatment. At onset, median WBC and PLT counts were 78.4 × 109/l (IR 34.0 – 135.9) and 399 × 109/l (IR 282 – 585), respectively. Sokal risk score was low in 52 patients (48.1%), intermediate in 49 (45.4%) and high in 7 (6.5%); a short pre-treatment phase (< 3 months) with Hydroxyurea was administered to 94/108 patients (87%). After 3 months of Imatinib treatment, 84 patients (77.7%) achieved CCyR while 24 patients (22.3%) still presented Ph+ metaphases (median value 40%, IR 20 - 80) at cytogenetic analysis. At univariate analysis, factors with a negative prognostic impact on achievement of CCyR at 3 months were palpable spleen enlargement (p=0.002), WBC count at onset > 100.0 × 109/l (p=0.01) and pre-treatment with Hydroxyurea (p=0.032); on the contrary, sex, age, Sokal risk score and PLT value did not appear to affect early CCyR achievement. Among the 84 patients in CCyR after 3 months, there were 10 failures during follow-up (6 cytogenetic relapses, 2 molecular relapses and 2 evolution to blastic phase); among the 24 patients who did not achieve early CCyR, there were 12 failures during follow-up (9 primary resistances and 3 cytogenetic relapses). The difference in the incidence of failures during follow-up in the 2 groups was highly significant (p<0.001). In conclusion, the achievement of CCyR at 3 months seems unrelated to traditional prognostic factors (Sokal); furthermore, in our experience it appears to have an important prognostic role, as patients not achieving it showed a significantly higher rate of failures during the follow-up. Disclosures: No relevant conflicts of interest to declare.

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