Patients not in complete cytogenetic response (CCyR) continuously face the competing possibilitie... more Patients not in complete cytogenetic response (CCyR) continuously face the competing possibilities of eventually achieving a cytogenetic response versus progressing. We analyzed the probability of achieving a CCyR, major molecular response, and progression in 258 patients with chronic myeloid leukemia in early chronic phase at 3, 6, and 12 months from imatinib start. The initial imatinib dose was 800 mg/day in 208 (81%) and 400 mg/day in 50 (19%) patients. For patients not in CCyR, the probability of achieving CCyR (P = .002) or major molecular response (P = .004) significantly decreased, whereas the risk of progression increased (P = .16) at each time point. Patients with a BCR-ABL1/ABL1 ratio greater than 1% to 10% after 3 months of imatinib had a 92% probability of achieving CCyR with continued therapy, similar to the 98% for those with 1% or less, but their risk of progression (11%) was almost 3-fold that of patients with a BCR-ABL1/ABL1 transcript ratio of 1% or less (4%) and s...
BACKGROUND. The effect on prognosis of adding imatinib mesylate to the treatment of patients with... more BACKGROUND. The effect on prognosis of adding imatinib mesylate to the treatment of patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) has not been explored fully. The objective of the current study was to evaluate the benefit of adding imatinib to the treatment sequence of patients with early chronic phase Ph-positive CML who received interferon ␣ (IFN)-based regimens as frontline therapy.
Cytogenetic clonal evolution (CE) is a known poor prognostic factor in Philadelphia chromosome-po... more Cytogenetic clonal evolution (CE) is a known poor prognostic factor in Philadelphia chromosome-positive chronic myelogenous leukemia (Ph-positive CML). However, its prognostic relevance in the era of imatinib therapy is unknown. We investigated the independent prognostic relevance of CE in 498 patients with Ph-positive CML treated with imatinib for chronic or accelerated phases. One hundred twenty-one patients had CE alone (n = 70) or with other accelerated phase criteria (n = 51). Patients were compared in 4 categories: chronic phase (n = 295), CE only (n = 70), accelerated phase without CE (n = 82), and accelerated phase with CE (n = 51). Statistical methods used established methodologies for univariate and multivariate analyses. In chronic and accelerated phases of CML, CE was not associated with significant differences in major or complete cytogenetic response rates, but it was an independent poor prognostic factor for survival by multivariate analyses in both chronic (P =.005) and accelerated phase (P =.03). Multivariate analyses conducted at the 3-month landmark (including the 3-month cytogenetic response) identified the lack of cytogenetic response at 3 months to be a stronger independent poor prognostic factor for survival than CE for both chronic (major cytogenetic response versus other) and accelerated phase (any cytogenetic response versus other). We conclude that cytogenetic CE is not an important factor for achieving major or complete cytogenetic response with imatinib mesylate therapy, but it is an independent poor prognostic factor for survival in both chronic and accelerated phases of CML. The 3-month cytogenetic response to imatinib mesylate refined the prognostic relevance of such studies in patients on imatinib mesylate therapy.
Clinical Cancer Research an Official Journal of the American Association For Cancer Research, Jul 1, 2002
Experimental Design: We treated 237 patients (median age, 50 years; age range, 18 -82 years) with... more Experimental Design: We treated 237 patients (median age, 50 years; age range, 18 -82 years) with Philadelphia chromosome (Ph)-positive accelerated-phase CML with oral imatinib mesylate at daily doses of 400 mg (26 patients) or 600 mg (211 patients) and evaluated response and survival characteristics in univariate and multivariate analyses.
A prospective randomized international study of 143 patients showed no apparent early survival ad... more A prospective randomized international study of 143 patients showed no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy. Combinations of alpha-interferon (INF) and chemotherapeutic agents are currently first-line therapy for the majority of patients with chronic myeloid leukemia (CML). The International Oncology Study Group conducted a prospective randomized study comparing INF combined with hydroxyurea or cytarabine. The primary study aim was to compare the survival durations in these patient cohorts. Patients with early chronic phase CML were randomized to receive INF 5 million units (Mu) given five times per week subcutaneously plus hydroxyurea or cytarabine as required to achieve a complete hematologic response and to maintain a WBC count between 2x10(9)/L and 10x10(9)/L and a platelet count between 75x10(9)/L and 100x10(9)/L. Therapy continued as tolerated unless progressive or blast phase disease occurred. At 36 months, the actuarial survival rate was equivalent in both groups: HI group (79 patients) survival was 85% (95% CI, 68-100%), as compared to 95% (95% CI, 79-100%) in the CI group (64 patients). In conclusion if seems that there is no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy.
We investigated whether increasing the dose of imatinib mesylate might overcome drug resistance i... more We investigated whether increasing the dose of imatinib mesylate might overcome drug resistance in patients with Philadelphia chromosome-positive (Ph(+)) chronic myelogenous leukemia (CML) whose disease manifests relapse or refractoriness to therapy. Fifty-four patients with Ph(+) CML in chronic phase and with hematologic or cytogenetic resistance or relapse on imatinib mesylate therapy at 400 mg orally daily were treated with a higher dose of 400 mg orally twice daily (800 mg daily, 47 patients; or 600 mg daily increased from 300 mg daily, 7 patients). Among 20 patients treated for hematologic resistance or relapse, 13 (65%) achieved a complete (n = 9) or partial (n = 4) hematologic response, but only 1 had a cytogenetic partial response (Ph reduction from 100% to 10%) and 1 had a minor response (Ph reduction from 100% to 50%). Among 34 patients treated for cytogenetic resistance or relapse, 19 (56%) achieved a complete (n = 6) or partial (n = 7) cytogenetic response. We conclude that higher doses of imatinib mesylate may overcome disease-poor response to conventional doses and that this approach deserves further evaluation as frontline therapy for newly diagnosed CML.
The purpose of our investigation was to evaluate the response and minimal residual disease by qua... more The purpose of our investigation was to evaluate the response and minimal residual disease by quantitative competitive PCR (QC-PCR) studies in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate.
Imatinib mesylate (STI571) is effective in chronic phase chronic myelogenous leukemia (CML). Howe... more Imatinib mesylate (STI571) is effective in chronic phase chronic myelogenous leukemia (CML). However, most patients treated with 400 mg imatinib daily have variable levels of residual molecular disease. We treated 114 patients with newly diagnosed chronic phase CML with 400 mg imatinib twice daily. Overall, 109 patients (96%) had a major cytogenetic response (Philadelphia chromosome [Ph] < 35%), and 103 (90%) had a complete response (Ph 0%). With a median follow-up of 15 months, no patient has progressed to accelerated or blastic phase. The estimated 2-year survival rate was 94%. By quantitative polymerase chain reaction (QPCR) studies, 71 (63%) of 112 patients showed BCR-ABL/ABL percentage ratios decrease to less than 0.05%, and 31 (28%) to undetectable levels. Compared with standard-dose imatinib, high-dose imatinib was associated with significantly better complete cytogenetic response (P ؍ .0005), major molecular response (QPRC < 0.05%; P ؍ .00001), and complete molecular response (undetectable BCR-ABL; P ؍ .001). High-dose imatinib was well tolerated but resulted in more frequent myelosuppression; 82% of patients continue to receive 600 mg or more of imatinib daily. In conclusion, high-dose imatinib induced higher rates of complete cytogenetic response and of molecular response in patients with newly diagnosed chronic phase CML. (Blood. 2004;
Purpose: The purpose of this research was to compare the survival of patients with Philadelphia c... more Purpose: The purpose of this research was to compare the survival of patients with Philadelphia chromosome (Ph) -positive chronic myelogenous leukemia (CML) post-IFN-␣ failure treated with imatinib to historical experiences with standards of care or other therapies. Experimental Design: The outcome of 261 patients with Ph-positive chronic phase CML post-IFN failure treated with imatinib was compared with 204 historical control patients treated for a similar disease status with existing therapies. A subset of 147 patients in late chronic phase CML and 100% Ph-positive status treated with imatinib was compared with 95 patients in a similar disease status treated with IFN. Multivariate analyses were conducted to assess the independent prognostic effect of therapy (imatinib versus other) on survival.
Purpose: The purpose of this research was to compare the survival of patients with Philadelphia c... more Purpose: The purpose of this research was to compare the survival of patients with Philadelphia chromosome (Ph) -positive chronic myelogenous leukemia (CML) post-IFN-␣ failure treated with imatinib to historical experiences with standards of care or other therapies. Experimental Design: The outcome of 261 patients with Ph-positive chronic phase CML post-IFN failure treated with imatinib was compared with 204 historical control patients treated for a similar disease status with existing therapies. A subset of 147 patients in late chronic phase CML and 100% Ph-positive status treated with imatinib was compared with 95 patients in a similar disease status treated with IFN. Multivariate analyses were conducted to assess the independent prognostic effect of therapy (imatinib versus other) on survival.
Journal of Clinical Oncology Official Journal of the American Society of Clinical Oncology, Feb 1, 2010
The current classification systems of myelodysplastic syndromes (MDS), including the Internationa... more The current classification systems of myelodysplastic syndromes (MDS), including the International Prognostic Scoring System (IPSS), do not fully reflect the molecular heterogeneity of the disease. Molecular characterization may predict clinical outcome and help stratify patients for targeted therapies. Epigenetic therapy using decitabine, a DNA hypomethylating agent, is clinically effective for the treatment of MDS. Therefore, we investigated the association between DNA methylation and clinical outcome in MDS.
Twenty-eight adults with chronic myelogenous leukemia (CML) that had relapsed after allogeneic st... more Twenty-eight adults with chronic myelogenous leukemia (CML) that had relapsed after allogeneic stem cell transplantation (SCT) received imatinib mesylate (400-1000 mg/d). Disease was in chronic phase in 5 patients, accelerated in 15, and blastic in 8 (7 medullary, 1 extramedullary); median time from transplantation to relapse was 9 months (range, 1-137 months). Thirteen patients had undergone salvage donor lymphocyte infusion (DLI) (median time from DLI to imatinib mesylate therapy, 4 months [range, 2-39 months]). The overall response rate was 79% (22 of 28 patients); the complete hematologic response (CHR) rate was 74% (17 of 23 patients), and the cytogenetic response rate was 58% (15 of 26 patients; complete response in 9 [35%] patients). CHR rates were 100% for chronic phase, 83% for accelerated phase, and 43% for blastic phase. The patient with extramedullary blastic disease achieved complete response. Cytogenetic response rates were 63% (12 of 19 patients) for chronic or accele...
One hundred and ten patients with Philadelphia chromosome (Ph)-positive chronic phase chronic mye... more One hundred and ten patients with Philadelphia chromosome (Ph)-positive chronic phase chronic myelogenous leukemia (CML) post-interferon-a failure treated with imatinib mesylate therapy were analyzed for the prognostic significance of marrow reticulin stain-measured fibrosis. The median time from diagnosis was 31 months. Severe reticulin (grade 3 - 4) fibrosis was observed in 67 patients (61%). Patients with severe marrow fibrosis had similar complete cytogenetic response rates with imatinib (67 vs. 58%; P = 0.45) compared with those with mild?-?moderate fibrosis. The estimated 4 year survival rates (80 vs. 88%; P = 0.27) and failure-free survival rates (69 vs. 77%; P = 0.34) were also not different. We conclude that the previously established poor prognostic significance of marrow fibrosis in CML is less relevant with imatinib therapy.
We propose a prognostic model specific to patients with therapy-related myelodysplastic syndrome ... more We propose a prognostic model specific to patients with therapy-related myelodysplastic syndrome (t-MDS). This model identifies three distinct survival groups among patients with t-MDS. The model is applicable in routine clinical practice and might facilitate the development of risk-adapted therapeutic strategies. Introduction/Background: We evaluated the characteristics of a cohort of patients with myelodysplastic syndrome (MDS) related to therapy (t-MDS) to create a prognostic model. Patients and Methods: We identified 281 patients with MDS who had received previous chemotherapy and/or radiotherapy for previous malignancy. Potential prognostic factors were determined using univariate and multivariate analyses. Results: Multivariate Cox regression analysis identified 7 factors that independently predicted short survival in t-MDS: age ! 65 years (hazard ratio [HR], 1.63), Eastern Cooperative Oncology Group performance status 2-4 (HR, 1.86), poor cytogenetics (À7 and/or complex; HR, 2.47), World Health Organization MDS subtype (RARs or RAEB-1/2; HR, 1.92), hemoglobin (< 11 g/dL; HR, 2.24), platelets (< 50 Â 10 9 /dL; HR, 2.01), and transfusion dependency (HR, 1.59). These risk factors were used to create a prognostic model that segregated patients into 3 groups with distinct median overall survival: good (0-2 risk factors; 34 months), intermediate (3-4 risk factors; 12 months), and poor (5-7 risk factors; 5 months) (P < .001) and 1-year leukemia-free survival (96%, 84%, and 72%, respectively, P ¼ .003). This model also identified distinct survival groups according to t-MDS therapy. Conclusion: In summary, we devised a prognostic model specifically for patients with t-MDS that predicted overall survival and leukemia-free survival. This model might facilitate the development of risk-adapted therapeutic strategies.
The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of a... more The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.
Patients not in complete cytogenetic response (CCyR) continuously face the competing possibilitie... more Patients not in complete cytogenetic response (CCyR) continuously face the competing possibilities of eventually achieving a cytogenetic response versus progressing. We analyzed the probability of achieving a CCyR, major molecular response, and progression in 258 patients with chronic myeloid leukemia in early chronic phase at 3, 6, and 12 months from imatinib start. The initial imatinib dose was 800 mg/day in 208 (81%) and 400 mg/day in 50 (19%) patients. For patients not in CCyR, the probability of achieving CCyR (P = .002) or major molecular response (P = .004) significantly decreased, whereas the risk of progression increased (P = .16) at each time point. Patients with a BCR-ABL1/ABL1 ratio greater than 1% to 10% after 3 months of imatinib had a 92% probability of achieving CCyR with continued therapy, similar to the 98% for those with 1% or less, but their risk of progression (11%) was almost 3-fold that of patients with a BCR-ABL1/ABL1 transcript ratio of 1% or less (4%) and s...
BACKGROUND. The effect on prognosis of adding imatinib mesylate to the treatment of patients with... more BACKGROUND. The effect on prognosis of adding imatinib mesylate to the treatment of patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) has not been explored fully. The objective of the current study was to evaluate the benefit of adding imatinib to the treatment sequence of patients with early chronic phase Ph-positive CML who received interferon ␣ (IFN)-based regimens as frontline therapy.
Cytogenetic clonal evolution (CE) is a known poor prognostic factor in Philadelphia chromosome-po... more Cytogenetic clonal evolution (CE) is a known poor prognostic factor in Philadelphia chromosome-positive chronic myelogenous leukemia (Ph-positive CML). However, its prognostic relevance in the era of imatinib therapy is unknown. We investigated the independent prognostic relevance of CE in 498 patients with Ph-positive CML treated with imatinib for chronic or accelerated phases. One hundred twenty-one patients had CE alone (n = 70) or with other accelerated phase criteria (n = 51). Patients were compared in 4 categories: chronic phase (n = 295), CE only (n = 70), accelerated phase without CE (n = 82), and accelerated phase with CE (n = 51). Statistical methods used established methodologies for univariate and multivariate analyses. In chronic and accelerated phases of CML, CE was not associated with significant differences in major or complete cytogenetic response rates, but it was an independent poor prognostic factor for survival by multivariate analyses in both chronic (P =.005) and accelerated phase (P =.03). Multivariate analyses conducted at the 3-month landmark (including the 3-month cytogenetic response) identified the lack of cytogenetic response at 3 months to be a stronger independent poor prognostic factor for survival than CE for both chronic (major cytogenetic response versus other) and accelerated phase (any cytogenetic response versus other). We conclude that cytogenetic CE is not an important factor for achieving major or complete cytogenetic response with imatinib mesylate therapy, but it is an independent poor prognostic factor for survival in both chronic and accelerated phases of CML. The 3-month cytogenetic response to imatinib mesylate refined the prognostic relevance of such studies in patients on imatinib mesylate therapy.
Clinical Cancer Research an Official Journal of the American Association For Cancer Research, Jul 1, 2002
Experimental Design: We treated 237 patients (median age, 50 years; age range, 18 -82 years) with... more Experimental Design: We treated 237 patients (median age, 50 years; age range, 18 -82 years) with Philadelphia chromosome (Ph)-positive accelerated-phase CML with oral imatinib mesylate at daily doses of 400 mg (26 patients) or 600 mg (211 patients) and evaluated response and survival characteristics in univariate and multivariate analyses.
A prospective randomized international study of 143 patients showed no apparent early survival ad... more A prospective randomized international study of 143 patients showed no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy. Combinations of alpha-interferon (INF) and chemotherapeutic agents are currently first-line therapy for the majority of patients with chronic myeloid leukemia (CML). The International Oncology Study Group conducted a prospective randomized study comparing INF combined with hydroxyurea or cytarabine. The primary study aim was to compare the survival durations in these patient cohorts. Patients with early chronic phase CML were randomized to receive INF 5 million units (Mu) given five times per week subcutaneously plus hydroxyurea or cytarabine as required to achieve a complete hematologic response and to maintain a WBC count between 2x10(9)/L and 10x10(9)/L and a platelet count between 75x10(9)/L and 100x10(9)/L. Therapy continued as tolerated unless progressive or blast phase disease occurred. At 36 months, the actuarial survival rate was equivalent in both groups: HI group (79 patients) survival was 85% (95% CI, 68-100%), as compared to 95% (95% CI, 79-100%) in the CI group (64 patients). In conclusion if seems that there is no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy.
We investigated whether increasing the dose of imatinib mesylate might overcome drug resistance i... more We investigated whether increasing the dose of imatinib mesylate might overcome drug resistance in patients with Philadelphia chromosome-positive (Ph(+)) chronic myelogenous leukemia (CML) whose disease manifests relapse or refractoriness to therapy. Fifty-four patients with Ph(+) CML in chronic phase and with hematologic or cytogenetic resistance or relapse on imatinib mesylate therapy at 400 mg orally daily were treated with a higher dose of 400 mg orally twice daily (800 mg daily, 47 patients; or 600 mg daily increased from 300 mg daily, 7 patients). Among 20 patients treated for hematologic resistance or relapse, 13 (65%) achieved a complete (n = 9) or partial (n = 4) hematologic response, but only 1 had a cytogenetic partial response (Ph reduction from 100% to 10%) and 1 had a minor response (Ph reduction from 100% to 50%). Among 34 patients treated for cytogenetic resistance or relapse, 19 (56%) achieved a complete (n = 6) or partial (n = 7) cytogenetic response. We conclude that higher doses of imatinib mesylate may overcome disease-poor response to conventional doses and that this approach deserves further evaluation as frontline therapy for newly diagnosed CML.
The purpose of our investigation was to evaluate the response and minimal residual disease by qua... more The purpose of our investigation was to evaluate the response and minimal residual disease by quantitative competitive PCR (QC-PCR) studies in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate.
Imatinib mesylate (STI571) is effective in chronic phase chronic myelogenous leukemia (CML). Howe... more Imatinib mesylate (STI571) is effective in chronic phase chronic myelogenous leukemia (CML). However, most patients treated with 400 mg imatinib daily have variable levels of residual molecular disease. We treated 114 patients with newly diagnosed chronic phase CML with 400 mg imatinib twice daily. Overall, 109 patients (96%) had a major cytogenetic response (Philadelphia chromosome [Ph] < 35%), and 103 (90%) had a complete response (Ph 0%). With a median follow-up of 15 months, no patient has progressed to accelerated or blastic phase. The estimated 2-year survival rate was 94%. By quantitative polymerase chain reaction (QPCR) studies, 71 (63%) of 112 patients showed BCR-ABL/ABL percentage ratios decrease to less than 0.05%, and 31 (28%) to undetectable levels. Compared with standard-dose imatinib, high-dose imatinib was associated with significantly better complete cytogenetic response (P ؍ .0005), major molecular response (QPRC < 0.05%; P ؍ .00001), and complete molecular response (undetectable BCR-ABL; P ؍ .001). High-dose imatinib was well tolerated but resulted in more frequent myelosuppression; 82% of patients continue to receive 600 mg or more of imatinib daily. In conclusion, high-dose imatinib induced higher rates of complete cytogenetic response and of molecular response in patients with newly diagnosed chronic phase CML. (Blood. 2004;
Purpose: The purpose of this research was to compare the survival of patients with Philadelphia c... more Purpose: The purpose of this research was to compare the survival of patients with Philadelphia chromosome (Ph) -positive chronic myelogenous leukemia (CML) post-IFN-␣ failure treated with imatinib to historical experiences with standards of care or other therapies. Experimental Design: The outcome of 261 patients with Ph-positive chronic phase CML post-IFN failure treated with imatinib was compared with 204 historical control patients treated for a similar disease status with existing therapies. A subset of 147 patients in late chronic phase CML and 100% Ph-positive status treated with imatinib was compared with 95 patients in a similar disease status treated with IFN. Multivariate analyses were conducted to assess the independent prognostic effect of therapy (imatinib versus other) on survival.
Purpose: The purpose of this research was to compare the survival of patients with Philadelphia c... more Purpose: The purpose of this research was to compare the survival of patients with Philadelphia chromosome (Ph) -positive chronic myelogenous leukemia (CML) post-IFN-␣ failure treated with imatinib to historical experiences with standards of care or other therapies. Experimental Design: The outcome of 261 patients with Ph-positive chronic phase CML post-IFN failure treated with imatinib was compared with 204 historical control patients treated for a similar disease status with existing therapies. A subset of 147 patients in late chronic phase CML and 100% Ph-positive status treated with imatinib was compared with 95 patients in a similar disease status treated with IFN. Multivariate analyses were conducted to assess the independent prognostic effect of therapy (imatinib versus other) on survival.
Journal of Clinical Oncology Official Journal of the American Society of Clinical Oncology, Feb 1, 2010
The current classification systems of myelodysplastic syndromes (MDS), including the Internationa... more The current classification systems of myelodysplastic syndromes (MDS), including the International Prognostic Scoring System (IPSS), do not fully reflect the molecular heterogeneity of the disease. Molecular characterization may predict clinical outcome and help stratify patients for targeted therapies. Epigenetic therapy using decitabine, a DNA hypomethylating agent, is clinically effective for the treatment of MDS. Therefore, we investigated the association between DNA methylation and clinical outcome in MDS.
Twenty-eight adults with chronic myelogenous leukemia (CML) that had relapsed after allogeneic st... more Twenty-eight adults with chronic myelogenous leukemia (CML) that had relapsed after allogeneic stem cell transplantation (SCT) received imatinib mesylate (400-1000 mg/d). Disease was in chronic phase in 5 patients, accelerated in 15, and blastic in 8 (7 medullary, 1 extramedullary); median time from transplantation to relapse was 9 months (range, 1-137 months). Thirteen patients had undergone salvage donor lymphocyte infusion (DLI) (median time from DLI to imatinib mesylate therapy, 4 months [range, 2-39 months]). The overall response rate was 79% (22 of 28 patients); the complete hematologic response (CHR) rate was 74% (17 of 23 patients), and the cytogenetic response rate was 58% (15 of 26 patients; complete response in 9 [35%] patients). CHR rates were 100% for chronic phase, 83% for accelerated phase, and 43% for blastic phase. The patient with extramedullary blastic disease achieved complete response. Cytogenetic response rates were 63% (12 of 19 patients) for chronic or accele...
One hundred and ten patients with Philadelphia chromosome (Ph)-positive chronic phase chronic mye... more One hundred and ten patients with Philadelphia chromosome (Ph)-positive chronic phase chronic myelogenous leukemia (CML) post-interferon-a failure treated with imatinib mesylate therapy were analyzed for the prognostic significance of marrow reticulin stain-measured fibrosis. The median time from diagnosis was 31 months. Severe reticulin (grade 3 - 4) fibrosis was observed in 67 patients (61%). Patients with severe marrow fibrosis had similar complete cytogenetic response rates with imatinib (67 vs. 58%; P = 0.45) compared with those with mild?-?moderate fibrosis. The estimated 4 year survival rates (80 vs. 88%; P = 0.27) and failure-free survival rates (69 vs. 77%; P = 0.34) were also not different. We conclude that the previously established poor prognostic significance of marrow fibrosis in CML is less relevant with imatinib therapy.
We propose a prognostic model specific to patients with therapy-related myelodysplastic syndrome ... more We propose a prognostic model specific to patients with therapy-related myelodysplastic syndrome (t-MDS). This model identifies three distinct survival groups among patients with t-MDS. The model is applicable in routine clinical practice and might facilitate the development of risk-adapted therapeutic strategies. Introduction/Background: We evaluated the characteristics of a cohort of patients with myelodysplastic syndrome (MDS) related to therapy (t-MDS) to create a prognostic model. Patients and Methods: We identified 281 patients with MDS who had received previous chemotherapy and/or radiotherapy for previous malignancy. Potential prognostic factors were determined using univariate and multivariate analyses. Results: Multivariate Cox regression analysis identified 7 factors that independently predicted short survival in t-MDS: age ! 65 years (hazard ratio [HR], 1.63), Eastern Cooperative Oncology Group performance status 2-4 (HR, 1.86), poor cytogenetics (À7 and/or complex; HR, 2.47), World Health Organization MDS subtype (RARs or RAEB-1/2; HR, 1.92), hemoglobin (< 11 g/dL; HR, 2.24), platelets (< 50 Â 10 9 /dL; HR, 2.01), and transfusion dependency (HR, 1.59). These risk factors were used to create a prognostic model that segregated patients into 3 groups with distinct median overall survival: good (0-2 risk factors; 34 months), intermediate (3-4 risk factors; 12 months), and poor (5-7 risk factors; 5 months) (P < .001) and 1-year leukemia-free survival (96%, 84%, and 72%, respectively, P ¼ .003). This model also identified distinct survival groups according to t-MDS therapy. Conclusion: In summary, we devised a prognostic model specifically for patients with t-MDS that predicted overall survival and leukemia-free survival. This model might facilitate the development of risk-adapted therapeutic strategies.
The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of a... more The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.
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