A Disease Model to Predict the Long-Term Outcomes Associated with Treatments for Chronic Myelogenous Leukemia (CML).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4480-4480
Author(s):  
Matthew Taylor ◽  
Lily Lewis ◽  
Thomas Patton ◽  
Ishan Hirji ◽  
Catherine Davis
Keyword(s):  
Disease Model ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Utility Value ◽  
Term Survival ◽  
Entire Cohort ◽  
Life Years ◽  
The Mean

Abstract Abstract 4480 Introduction Dasatinib, a BCR-ABL inhibitor 325 fold more potent than imatinib, has been studied in DASISION a randomized comparison vs. imatinib in patients with newly diagnosed chronic phase CML. A computer simulation disease model was developed to examine long-term survival outcomes following treatment with dasatinib, imatinib, or nilotinib in this patient population. Methods A disease model was developed to estimate the lifetime health outcomes associated with each form of treatment. Five initial best-response categories were used (no response (NR), complete hematologic response (CHR), partial cytogenetic response (PCyR), complete cytogenetic response (CCyR) and molecular response (MR)), which were each linked to a disease prognosis based on previously published evidence. Mutually exclusive initial response rates for NR, CHR, PCyR, CCyR and MR came from the DASISION trial for dasatinib and imatinib while those for nilotinib were identified from published ENESTnd data. A quality of life (QoL) utility value was assigned to each health state (chronic phase with response, chronic phase without response, progressed, and dead), also from previous publications. Adverse events were accounted for in terms of their impact upon QoL utility values. Extrapolation beyond the published data was undertaken by calculating trend rates for the final three years of follow up and applying age related mortality rates. Uncertainty was incorporated into the analysis by fitting distributions to survival and using simulation techniques to run 1,000 iterations. The model calculated survival based on the mean number of years’ survival per patient, across the entire cohort. Adjusted QoL utility values were calculated by assigning a QoL utility value weight to each state (see above) and calculating the mean total outcome for the entire cohort. Incremental survival was calculated by comparing the mean survival associated with each treatment. Results The quality adjusted life years (QALYs) and life years (LYs) are given in Table 1. The QALYs and LYs were 12.238 and 14.727 for dasatinib, 11.506 and 13.822 for imatinib and 12.016 and 14.426 for nilotinib, respectively. Conclusion Based on simulation modeling, results suggest that treatment with dasatinib may be associated with long-term survival as well as QoL-adjusted survival benefits. Long-term follow-up of ongoing studies will be needed to confirm these predicted benefits. Disclosures: Taylor: Bristol Myers-Squibb: Consultancy. Lewis:Bristol Myers-Squibb: Consultancy. Patton:Bristol Myers-Squibb: Consultancy. Hirji:Bristol Myers-Squibb: Employment. Davis:Bristol Myers-Squibb: Employment.

scholarly journals Clinical results of the Metha short hip stem: a perspective for younger patients?

2013 ◽  
Vol 5 (4) ◽  
pp. 34 ◽  
Author(s):  
Fritz Thorey ◽  
Claudia Hoefer ◽  
Nima Abdi-Tabari ◽  
Matthias Lerch ◽  
Stefan Budde ◽  
...  
Keyword(s):  
Bone Ingrowth ◽  
Long Term Results ◽  
Harris Hip Score ◽  
Femoral Revision ◽  
Term Survival ◽  
Younger Patients ◽  
The Mean ◽  
Short Stems

In recent years, various uncemented proximal metaphyseal hip stems were introduced for younger patients as a bone preserving strategy. Initial osteodensitometric analyses of the surrounding bone of short stems indicate an increase of bone mass with secondary bone ingrowth fixation as a predictor of long-term survival of these types of implants. We report the outcome of 151 modular Metha short hip stem implants in 148 patients between March 2005 and October 2007. The mean follow-up was 5.8±0.7 years and the mean age of the patients was 55.7±9.8 years. Along with demographic data and co-morbidities, the Harris Hip Score (HHS), the Hip dysfunction and Osteoarthritis Outcome Score (HOOS), and also the results of a patient-administered questionnaire were recorded pre-operatively and at follow-up. The mean HHS increased from 46±17 pre-operatively to 90±5 the HOOS improved from 55±16 pre-operatively to 89±10 at the final follow-up. A total of three patients have been revised, two for subsidence with femoral revision and one for infection without femoral revision (Kaplan Meier survival estimate 98%). The radiological findings showed no radiolucent lines in any of the patients. The modular Metha short hip stem was implanted in younger patients, who reported an overall high level of satisfaction. The clinical and radiographic results give support to the principle of using short stems with metaphyseal anchorage. However, long-term results are necessary to confirm the success of this concept in the years to come.

scholarly journals Reconstruction of the Aortic Arch in Newborns and Infants Using an Extended End-to-End Anastomosis

2021 ◽  
pp. 63-68
Author(s):  
Iaroslav P. Truba ◽  
Ivan V. Dziuryi ◽  
Roman I. Sekelyk ◽  
Oleksandr S. Golovenko
Keyword(s):  
Hospital Mortality ◽  
Aortic Arch ◽  
Median Sternotomy ◽  
Term Survival ◽  
Long Term Survival ◽  
The Mean ◽  
End To End ◽  
Aortic Arch Hypoplasia

The problem of the effectiveness of obstruction at the level of the aortic arch is still a matter of discus-sion in the modern literature. Traditionally, by excision of the coarctation part, in the presence of hypoplasia, the incision is extended to a narrowed area and a modification of the classical end-to-end anastomosis is applied in the form of an elongated or expanded variant. Recently, when proximal part is involved in the pathological process, cardiac surgeons have been more likely to use median sternotomy using other types of plastic surgery, including dilation of the narrowed area with a pericardial patch, or pulmonary artery tissue. Accordingly, the analysis of the results of the use of end-to-end anastomosis in young children with aortic arch hypoplasia, especially in view of long-term survival and the level of reoperation, is an important issue of neonatal cardiac surgery. The aim. To evaluate the effectiveness of the use of an extended end-to-end anastomosis after reconstruction of the aortic arch in children under 1 year of age. Materials and methods. The study material included 348 infants who underwent surgical correction of aortic arch hypoplasia through the method of extended end-to-end anastomosis from 2010 to 2020. The operations were performed at the National Amosov Institute of Cardiovascular Surgery of the NAMS of Ukraine and the Ukrainian Children’s Cardiac Center. The study group included only patients with two-ventricular physiology. There were 233 male patients (67%) and 115 female patients (33%). The mean age was 1.07 (0.20; 2.30) months, the mean weight was 3.89 (3.30; 4.90) kg, the mean body surface area was 0.23 (0.20; 0.28) m2. Diagnosis of aortic arch hypoplasia was based on two-dimensional echocardiography. Results. According to echocardiography, after surgery there was a significant decrease in the pressure gradient in the aortic arch from 48.3 ± 20.3 to 16 ± 6.9 (p<0.05), left ventricular PV increased significantly from 61.6 ± 12% to 66.3 ± 6.4% (p> 0.05). The hospital mortality was 1.7% (n = 6). The causes of mortality were not related to the end-to-end aortic arch technique. The duration of follow-up period ranged from 1 month to 9.3 years. Two deaths occurred in the follow-up period. Thirty-two (9.1%) patients developed aortic arch restenosis in the postoperative period. Balloon dilatation of restenosis was performed in 21 patients. Eleven patients underwent repeated aortic arch repair surgery through the median sternotomy. There were no central nervous system complications in the follow-up period. Conclusions. The use of an extended end-to-end anastomosis in the surgical treatment of aortic arch hypoplasia demon strates low hospital mortality and high long-term survival. Indications for the effective use of this type of reconstruction are hypoplasia of the isthmus and distal aortic arch.

Imatinib in the Treatment of CML Patients ≥ 65 Years Old in Late Chronic Phase: Results of a Phase II Study of the GIMEMA CML Working Party.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2935-2935
Author(s):  
Simona Bassi ◽  
Fausto Castagnetti ◽  
Marilina Amabile ◽  
Barbara Giannini ◽  
Daniela Cilloni ◽  
...  
Keyword(s):  
Adverse Events ◽  
Older Patients ◽  
Age Groups ◽  
Chronic Phase ◽  
Working Party ◽  
Cytogenetic Response ◽  
Term Survival ◽  
Grade Iii ◽  
Two Age Groups

Abstract Older age constitutes a poor prognostic variable in CML patients: the negative effect of age on long-term survival has been consistently observed with most effective therapeutic modalities, both drug therapies (busulfan, hydroxyurea and interferon) and allogeneic transplant. In particular, older patients treated with interferon experienced much more adverse events than younger ones. In part their poorer prognosis was probably due to poor treatment compliance and few older patients have been included in prospective studies of interferon. Actually, imatinib is the first-line treatment for CML: its efficacy is very high and it seems to be well tolerated across age groups. We performed a sub-analysis of the effects of age on response and tolerance within the phase II trial of the italian GIMEMA CML Working Party (serial n.CML/002/STI571), which included 284 late chronic phase patients, treated with imatinib (400 mg daily) after interferon failure. Following the WHO, who defines “old” a patient ≥ 65 years, we analyzed the safety and efficacy of imatinib by age group: 226/284 patients (80%) were &lt; 65 years (extr. 17–64) and 58/284 (20%) were ≥ 65 years (extr. 65–85 yrs) old. No significant differences between the two age groups were present at enrollment. Table 1 shows the responses and incidence of hematologic and non-hematologic adverse events (AEs). As expected, older patients experienced more AEs, both hematologic and non-hematologic. In part this significantly poorer tolerance probably justifies the lower response rates, both hematologic and cytogenetic. However, the overall survival was not different between the two age groups: with a median observation time of 33 months, the overall survival curves were superimposed (91%). Moreover, the rate of progression to accelerated/blastic phase was the same (10%). This study demonstrates that imatinib is greatly effective in older CML patients in late chronic phase (53% of MCR and 36% of CCR) and allows a good long-term survival. It is conceivable that treating old CML patients at the onset of the disease, as already shown by Jorge Cortes et al (Cancer2003;98:1105), could translate into response rates as the ones of younger patients. Responses and adverse events ≥ 65 (n. 58) ≤ 65 (n226) p value Complete Hematologic response 91% 99% 0,001 Major Cytogenetic Response 53% 74% 0,003 Complete Cytogenetic Response 36% 57% 0,001 Grade III Hematologic AEs 72% 50% 0,002 Grade III+IV Hematologic AEs 86% 60% 0,0001 Grade II non Hematologic AEs 83% 68% 0,0001 Grade III + IV non Hematologic AEs 29% 10% 0,0001

Imatinib Dose Escalation Is Effective in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1047-1047
Author(s):  
Hagop M. Kantarjian ◽  
Brian J. Druker ◽  
Francois Guilhot ◽  
Jorge Cortes ◽  
Stephen G. O’Brien ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Randomized Study ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Separate Analysis ◽  
Inadequate Response ◽  
Durable Response ◽  
Entire Cohort ◽  
The Impact

Abstract Background: Imatinib mesylate (IM) 400 mg/d is the standard of care for newly diagnosed patients (pts) with CML-CP. Dose escalation to 600 or 800 mg IM has been shown to be beneficial in patients with either an inadequate response or disease progression while on standard therapy (Kantarjian et al Blood 2003). In the International Randomized study of Interferon versus STI571 (IRIS) trial, initiated in 2000, dose escalation was allowed for patients who did not achieve a complete hematologic response (CHR) by 3 months or a minor cytogenetic response (minCyR) by 12 months, lost a major cytogenetic response (MCyR) at any time, or progressed (including increase in WBC); no dose escalation in cases of loss of CCyR were specified. The impact of IM dose escalation for patients on IRIS is presented in this post-hoc analysis. Methods: Patients were evaluated for hematologic and cytogenetic responses, progression (to accelerated or blast phase) free survival (PFS), and overall survival (OS) following dose escalation. Patients were included if their dose was increased within −0.5 to 3 months following the respective landmark evaluation. Instances of dose escalation (to ≥600 mg/d) on the IM arm were reviewed and classified, where possible, based on either criteria established by IRIS protocol or the European LeukemiaNet recommendations Results: Of 551 patients receiving first line IM, 106 pts (19%) had dose escalation to 600–800 mg/d. Median time to dose escalation was 22 months (range:3–74 months; 25th–75th percentile: 13–45 months). After dose escalation the median imatinib dose delivered was 604 mg/d (range: 294–800 mg/d; 25th–75th percentile:600–739 mg/d) and remained on treatment for a median of 19.4 months based on current follow-up. Last recorded dose was ≥600mg/d in 85% of these patients. Dose increases in 39 patients were based on the IRIS protocol criteria. Responses among these patients included: 6 of 7 who had not achieved CHR at 3 months achieved a CHR with dose escalation, 2 of these patients subsequently achieved a CCyR. Of 8 patients who had not achieved a minCyR at 12 months, 4 improved to a CCyR, and of 18 patients who lost their MCyR, 9 subsequently re-achieved an MCyR within 12.5 months after dose escalation, of whom 3 also attained a CCyR by 30-months after dose escalation. The 6 patients who received dose escalations upon progression, had an OS of 83% at 2 years after dose escalation. At 36-months after dose escalation the 39 patients dose escalated per IRIS protocol criteria achieved an estimated PFS and OS of 81%. In a separate analysis of these 106 pts, dose escalations in 48 pts were retrospectively classified according to the ELN recommendations. At 36-months follow-up after dose escalation these 48 patients achieved a 90% PFS and 89% OS. For the entire cohort of 106 patients who were dose escalated, estimated PFS was 89% and OS was 84% at 36 months after dose escalation. Conclusion: Based on these data, IM dose escalation to 600 and/or 800 mg allows poorly responding patients to achieve a clinically important durable response or re-gain responses. These slower responding or progressing patients benefited from IM dose escalation and thus, the data support dose escalation for these patients.

IRIS 6-Year Follow-Up: Sustained Survival and Declining Annual Rate of Transformation in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Imatinib.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 25-25 ◽  
Author(s):  
Andreas Hochhaus ◽  
Brian J. Druker ◽  
Richard A. Larson ◽  
Stephen G. O’Brien ◽  
Insa Gathmann ◽  
...  
Keyword(s):  
Adverse Events ◽  
Blast Crisis ◽  
Randomized Study ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Continuous Treatment ◽  
Annual Rate ◽  
Interferon Α

Abstract Background: The International Randomized study of Interferon versus STI571 (IRIS) study demonstrated that imatinib has superior safety and efficacy relative to interferon-α plus cytarabine (IFN+ara-C). Patients on the imatinib arm achieved an estimated 5-year OS of 89%. To monitor the long-term responses achieved by patients on imatinib, the 6-year follow-up of the IRIS patient population is summarized. Methods: 1106 patients were randomly assigned to either imatinib or IFN+ara-C and evaluated for hematologic and cytogenetic responses, event-free survival, progression to accelerated-phase (AP) or blast crisis (BC), overall survival (OS), and frequency of adverse events and discontinuations. Results: The downward trend in the risk of disease progression on imatinib has continued with a 0.4% event rate (including loss of response) and a 0% rate of transformation to AP/BC attained between years 5 and 6. Of 553 who were randomized to imatinib, 364 (65.8%) remain on study drug at 6 years: 14 (2.5%) crossed over to the IFN arm, and 175 (31.6%) pts have discontinued from imatinib study therapy for any reason. The following reasons were cited for discontinuation from the IRIS study: adverse events, 23 patients (4.2%); unsatisfactory therapeutic effect, 66 patients (11.9%); protocol violation, 15 patients (2.7%); withdrawal of consent, 32 patients (5.8%); administrative problems, 6 patients (1.1%); and 16 patients (2.9%) elected to undergo a stem cell transplantation (SCT). Death was the reason for discontinuation for 10 (1.8%) patients, and 7 patients (1.3%) were lost to follow-up. The best observed complete hematologic response rate among patients receiving first-line imatinib was 97%. The best observed major cytogenetic response (MCyR) and complete cytogenetic response (CCyR) rates were 89% and 83%, respectively, with 2 additional CCyR observed since the prior 5-year analysis. At the current 6-year follow-up, 325 patients are still in CCyR, another 24 had lost CCyR but regained it, 6 patients lost CCyR but remain in MCyR, and the remaining 9 patients never had a documented CCyR. Overall, an estimated 83% of patients were event-free, and 93% were free of progression to AP or BC at 6 years on imatinib study treatment, as patients were followed only for OS after discontinuation. After the second year on imatinib, the annual rate of events decreased every year, as did the annual relapse rate. Based on the current follow-up, a total of 66 (12%) patients have died (19 after SCT, 27 not due to CML). Estimated 6-year OS rate for all patients who received imatinib as initial therapy was 88%. When survival is censored at time of SCT for patients who proceeded to transplant, the estimated OS at 6 years is 91%. In an analysis of serious adverse events, no new safety issues were identified between the 5-year report and this analysis. Conclusions: The 6-year follow-up analysis of the IRIS population indicates that continuous treatment of chronic-phase CML with imatinib induces durable responses in a high percentage of patients with a decreasing rate of relapse and a favorable long-term safety profile.

Landmark Analysis of Imatinib Treatment in CML Chronic Phase: ES-FISH <10% Ph+ At 3 Months Associated with Better Cytogenetic Response and Improved Long-Term Event-Free Survival

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1702-1702
Author(s):  
Anne-Charlotte Ohm ◽  
Gisela Barbany ◽  
Ingrid Arvidsson ◽  
Robert Hast ◽  
Leif Stenke
Keyword(s):  
Disease Progression ◽  
Early Treatment ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Similar Data ◽  
Term Survival ◽  
Expression Levels ◽  
Landmark Analysis ◽  
Landmark Analyses

Abstract Abstract 1702 The use of imatinib (ima) and other tyrosine kinase inhibitors (TKI) has dramatically improved the clinical outcome for patients (pts) with chronic myeloid leukemia in chronic phase (CMLcp). Although most pts respond well, there is a subpopulation that fails to reach internationally defined clinical treatment goals, as assessed by techniques such as cytogenetics (CG) and quantitative polymerase chain reaction (PCR). Pts with a poor initial treatment response appear to have an increased risk of subsequent disease progression to accelerated phase or blast crisis, which still constitute a serious medical challenge. It was recently shown that landmark analysis assessing PCR levels after 3 months (mo) of ima treatment was linked to major cytogenetic response (mCyR) at 12 mo and risk of long-term progression (Hanfstein ASH2010 abstract 360). Similar data based on fluorescence in-situ hybridization (FISH) landmark assessment of larger CMLcp pt groups are still lacking. We have followed a cohort of 45 newly diagnosed CMLcp pts, all initiated on ima (400mg qd), by sequentially assessing their treatment responses by CG, PCR and interphase ES-FISH and relating early BCR-ABL expression levels to subsequent clinical response. A complete cytogenetic response (CCyR) was observed in 56% of evaluable pts after 6 mo, 80% after 12 mo and 94% after 24 mo of treatment. Corresponding figures for major molecular response (MMR) were 9%, 47% and 71%, respectively. Early levels of BCR-ABL as assessed by FISH could predict subsequent response. Thus, of patients with FISH-pos ≤10% at 3 mo 95% achieved CCyR at 12 mo, while this response was noted in only 67% of pts with FISH-pos >10% at 3 mo (p=0.042; Fisher's exact test, n=37). Similarly, all evaluable pts with FISH-pos ≤10% at 3 mo were alive and event-free (EFS) at 36 mo, as compared to 67% EFS at 36 mo among pts with FISH-pos >10% at 3 mo (p=0.008, n=37). Performing similar landmark analyses with FISH ≤ or >10% at 6 and 12 mo also yielded significant differences regarding EFS at 36 mo (p=0.046 and p=0.003, respectively). Employing corresponding landmark analyses with PCR at 3 mo and 6 mo, no significant association to EFS at 36 mo could be detected. In conclusion, our landmark analysis data indicate that ES-FISH can be used effectively already after 3 mo of ima treatment in order to identify a patient cohort with inferior long-term survival and with a higher risk for disease progression. FISH can unlike CG, be efficiently performed on peripheral blood cells which facilitates its clinical use. In comparison to PCR earlier data have shown that FISH, although less sensitive, may be more reliable and reproducible at higher BCR-ABL expression levels, typically seen in the early treatment phase. This may explain the superior outcome of early landmark analysis using FISH, as compared to PCR, in our study. Expanded trials on larger CMLcp pt cohorts are warranted to further clarify the prognostic value, and possible impact on early treatment alterations, of early FISH analyses during TKI treatment. Disclosures: No relevant conflicts of interest to declare.

Nilotinib Versus High-Dose Imatinib in Early Chronic Phase CML Patients Who Have Suboptimal Molecular Responses to Standard-Dose Imatinib: Updated Data From RE-Nice Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3775-3775 ◽  
Author(s):  
Soo-Young Choi ◽  
Sung-Eun Lee ◽  
Soo-Hyun Kim ◽  
Eun-Jung Jang ◽  
Jin-hwa Lee ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Standard Dose ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
High Dose ◽  
Molecular Response ◽  
Long Term Outcomes ◽  
First Line

Abstract Abstract 3775 Background. In chronic myeloid leukemia (CML), achievement of optimal responses by time point has improved long-term outcomes. In contrast, several clinical studies investigating the clinical implications of suboptimal response showed that patients with suboptimal responses tend to have poor long-term outcomes. In IRIS study, patients who achieved major molecular response (MMR) at 18 months had event-free survival (EFS) benefit, compared to those who achieved complete cytogenetic response (CCyR) without MMR. However, the best treatment for these patients is still not confirmed. By the previous studies, sustaining standard-dose of imatinib (IM) is expected to yield less than 20 percent of additive MMR. In this prospective study, we investigated whether switching to nilotinib (NIL) or high-dose IM may be more effective for patients with suboptimal molecular response to IM as first-line therapy. Methods. Early chronic phase (CP) CML patients who have achieved CCyR but no MMR after at least 18 months and up to 24 months (≤ 18 to ≥24 months) on first-line IM therapy at a daily dose of 400 mg were enrolled in this clinical trial, and informed consents were obtained from all patients. In NIL arm, patients received oral dose of 400 mg BID (800 mg/day) and in high-dose IM arm, patients received 800 mg/day administrated as 400 mg BID. Primary endpoint is to evaluate the cumulative MMR rates by 12 months, and secondary endpoints are to evaluate the cumulative MMR, MR4.0 and undetectable molecular residual disease (UMRD) rates during further 24 month follow-up. Safety profiles will also be assessed. Patients showing lack of response (lack of complete hematologic response (CHR) at 6 months, increasing WBC, no major cytogenetic response (MCyR) at 24 months), loss of response (loss of CHR or MCyR) or severe intolerance to treatment were allowed to crossover to the alternative treatment. Results. With a data cut-off date of 10 Jul 2012, a total of 43 patients were randomized into NIL arm (n = 22) or high-dose IM arm (n = 21). With a median follow-up of 15 months (range, 1–36), all patients have maintained CCyR without progression to advanced disease, and progressive decrease in BCR-ABL1 transcript levels was observed in all patients. Cumulative incidence (CI) of MMR by 12 months showed no significant difference between NIL arm and high-dose IM arm (37.8 ± 11.9% vs 34.8 ± 10.6%, P = 0.789). In NIL arm, 3 in 22 (14%) and 2 in 22 (9%) patients achieved MR4.0 and UMRD, respectively, and in high-dose IM arm, 1 in 21 (5%) patients achieved MR4.0. Overall, the patients treated with high-dose IM showed toxicities more frequently, such as fatigue, dyspnea and decreased phosphate. In addition, 10 patients in high-dose IM arm have cross-over to NIL treatment due to lack of response (n=9) and intolerance (n=1), and the median duration of NIL treatment was 14 months (range, 7–26 months). Among them, 5 (50%) patients have achieved MMR with a median NIL treatment duration of 12 months (range, 3–18). Conclusions. These results demonstrate that early switching to NIL or dose escalation of IM could be recommended, considering the results of standard dose of IM in suboptimal molecular responders. When the tolerability of treatment was considered for switching to NIL or high-dose IM, NIL may be preferred. Through further clinical investigation on a large patient population and longer period observation, the efficacy and safety of early intervention of suboptimal molecular response using NIL or dose escalation of IM will be needed. Updated data with longer follow-up duration will be presented in the meeting. Disclosures: No relevant conflicts of interest to declare.

Significance of Suboptimal Response to Imatinib, as Defined by the European LeukemiaNet, in Long-Term Outcome for Patients (Pts) with Chronic Phase (CP) Chronic Myeloid Leukemia (CML).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1932-1932 ◽  
Author(s):  
Yesid Alvarado ◽  
Hagop Kantarjian ◽  
Stefan Faderl ◽  
Jan Burger ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Cytogenetic Response ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Complete Hematologic Response ◽  
Starting Dose ◽  
Prognostic Implications ◽  
Definition Of

Abstract The European LeukemiaNet recently published recommendations for evaluating response to imatinib among pts with CML. Criteria for failure and suboptimal responses were proposed. The significance of failure is accepted and constitutes grounds for change in treatment. The prognostic implications of having a suboptimal response are less clear making treatment decisions less clear in this setting. We analyzed the outcome of 281 pts treated with imatinib as frontline therapy for CML in CP: 73 at initial dose of 400mg daily and 208 at 800mg daily. Their median age was 48 yrs (range, 15 to 84 yrs) and their median follow-up 48 months (mo) (2–79 mo). After 3 mo of therapy none of the 273 evaluable pts met definition of suboptimal response according to the European LeukemiaNet, while 3 of 273 (1%) met definition for failure. At 6 mo 10/259 (4%) evaluable had suboptimal response and 9 (3%) failure. At 12 mo 19/246 (8%) had suboptimal and 14 (6%) failure, and at 18 mo 91/224 (41%) had suboptimal and 21 (9%) had failure. The probability of having a suboptimal response at 6 and 12 mo was significantly higher for pts treated with a starting dose of 400mg than those treated at 800mg: at 6 mo [12% suboptimal at 400mg vs 1% at 800mg (p=0.002)] and at 12 mo [17% and 4%, respectively (p&lt;0.001)]. The outcome at 24 months* by the response at specific times was as follows: Time Response % CCyR % MMR % Transf % Event CCyR=Complete cytogenetic remission, MMR=Major molecular remission, Transf=Transformation to accelerated or blast phase, Event=loss of complete hematologic response, loss of major cytogenetic response, transformation, or death 6 mo Optimal 91 60 2 6 Suboptimal 0 0 30 50 Failure 0 0 22 67 P .001 .001 .001 .001 12 mo Optimal 94 63 2 4 Suboptimal 56 25 0 16 Failure 0 0 21 57 P .001 .001 .001 .001 18 mo Optimal 98 85 0 1 Suboptimal 93 39 2 5 Failure 15 0 19 43 P .001 .001 .001 .001

Assessment of Early Cytogenetic Response As a Predictor of Long-Term Clinical Outcomes in a Phase 1/2 Study of Bosutinib in Chronic Phase CML.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2798-2798 ◽  
Author(s):  
Jorge E Cortes ◽  
Tim H Brümmendorf ◽  
H. Jean Khoury ◽  
Andreas Hochhaus ◽  
Jane Apperley ◽  
...  
Keyword(s):  
Research Funding ◽  
Phase 1 ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Advisory Committees ◽  
Kaplan Meier ◽  
Satellite Symposia ◽  
Time Point

Abstract Abstract 2798 Bosutinib (BOS) is an orally active, dual Src/Abl tyrosine kinase inhibitor (TKI). In an open-label, phase 1/2 trial BOS 500 mg/d demonstrated clinical activity and manageable toxicity in patients (pts) with chronic phase (CP) chronic myeloid leukemia (CML) following resistance/intolerance to imatinib (IM; Blood 2011;118:4567-76) and possibly dasatinib (DAS) and/or nilotinib (NI; Blood 2012;119:3403-12). This retrospective analysis investigated attainment/maintenance of major cytogenetic response (MCyR) by Months 3, 6, 9, and 12 as an early predictor of long-term outcomes in pts receiving bosutinib as second-line (CP 2L; after failure of IM only) or third/fourth-line (CP 3L; after failure of IM plus DAS and/or NIL) therapy for CP CML. Pts aged 318 y with CP CML received oral BOS starting at 500 mg/d. A total of 288 CP 2L pts with IM resistance (n = 200) or intolerance (n = 88) were enrolled: 53% were male, median age was 53 y (range, 18–91 y), and median time from CML diagnosis was 3.6 y (range, 0.1–15.1 y). A total of 119 CP 3L pts were enrolled following failure of IM plus resistance to DAS (n = 38), intolerance to DAS (n = 50), resistance to NIL (n = 27), intolerance to NIL (n = 1), or resistance/intolerance to DAS and NIL (n = 3): 45% were male, median age was 56 y (range, 20–79 y), and median time from CML diagnosis was 6.5 y (range, 0.6–18.3 y). Median treatment duration was 22.1 mo (range, 0.2–60.8 mo) for CP 2L pts and 8.6 mo (range, 0.2–60.8 mo) for CP 3L pts. Time from the last enrolled pt's first dose to the data cutoff was 23 mo for CP 2L pts, with a median follow-up duration of 31.8 mo (range, 0.6–66.0 mo). Time from the last pt's first dose to the data cutoff was 25 mo for CP 3L pts, with a median follow-up duration of 31.4 mo (range, 0.3– 66.0 mo). Among the 266 CP 2L pts who had a valid baseline cytogenetic assessment, a MCyR was attained/maintained (improved baseline cytogenetic assessment and attained a MCyR, or maintained baseline MCyR post-baseline) by 108/186 (58%) IM-resistant and 49/80 (61%) IM-intolerant pts, including 85/186 (46%) and 43/80 (54%) pts, respectively, who attained/maintained a complete cytogenetic response (CCyR). Among pts without a CCyR at baseline, 103/181 (57%) IM-resistant and 39/69 (57%) IM-intolerant pts achieved a MCyR. The Kaplan-Meier probability of maintaining a MCyR at 2 y was 71% for IM-resistant and 88% for IM-intolerant pts. Among 110 CP 3L pts who had a valid baseline cytogenetic assessment, cumulative rates for attaining/maintaining a MCyR and CCyR were 41% and 32%, respectively. The Kaplan-Meier probability of maintaining a MCyR at 2 y was 71%. A landmark analysis showed that the attainment/maintenance of a MCyR by Months 6, 9, and 12 on treatment was associated with an increased likelihood of overall survival (OS) at 2 y for both CP 2L and CP 3L pts. The difference in OS between those with and without a MCyR reached significance by Month 3 for CP 2L pts but not until Month 6 for CP 3L pts (Table). In conclusion, early attainment or maintenance of a MCyR (by Month 3) correlated with better OS in CP CML pts treated with BOS following IM failure. In CP CML pts treated with BOS following failure of 32 TKIs, 2-y OS was not different in pts with and without a MCyR prior to the Month 6 time point. This suggests that it is acceptable to allow longer periods of treatment for these pts to achieve responses without imparting significant long-term detriment. MCyR No MCyR n evaluablea MCyR, n OS at 2 yb (95% CI) No MCyR, n OS at 2 yb (95% CI) P value for OSc CP 2L cohort By Month 3 282 96 98% (91.8–99.5) 186 88% (82.0–91.8) 0.005 By Month 6 277 126 97% (91.7–98.8) 151 88% (82.0–92.6) 0.011 By Month 9 275 141 96% (91.5–98.5) 134 89% (81.7–92.9) 0.009 By Month 12 272 151 96%(91.3–98.2) 121 90% (82.8–94.1) 0.016 CP 3L cohort By Month 3 115 28 88% (68.1–96.1) 87 86% (75.9–91.5) 0.232 By Month 6 112 40 92% (77.4–97.4) 72 84% (73.2–90.9) 0.027 By Month 9 108 40 95% (80.1–98.6) 68 88% (76.9–93.6) 0.022 By Month 12 103 40 95% (81.0–98.7) 63 89% (77.7–94.4) 0.023 a Pts known to be alive exceeding the respective landmark time point. b Kaplan-Meier estimate of OS is based on total follow-up of 2 y from first BOS dose (response by Month 3 and OS over next 21 mo; response by Month 6 and OS over next 18 mo; response by Month 9 and OS over next 15 mo; or response by Month 12 and OS over next 12 mo). c Kaplan-Meier log-rank test for comparison of pts attaining/maintaining a MCyR versus no MCyR. Disclosures: Cortes: Novartis, Bristol Myers Squibb, Pfizer, Ariad, Chemgenex: Consultancy, Research Funding. Brümmendorf:Bristol Myer Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; Patent on the use of imatinib and hypusination: Patents & Royalties. Hochhaus:Pfizer, Novartis, BMS, MSD, Ariad: Consultancy, Research Funding. Apperley:BMS, Teva, Ariad: Membership on an entity's Board of Directors or advisory committees; Pfizer, Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis and BMS: Speaker at satellite symposia, Speaker at satellite symposia Other. O'Brien:Pfizer Inc: Research Funding. Leip:Pfizer Inc: Employment. Kelly:Pfizer Inc: Employment, Equity Ownership. Ruffner:Pfizer Inc: Employment. Kantarjian:Pfizer Inc: Research Funding.

scholarly journals Mid-to Long-Term Survival of Total Knee Arthroplasty in Hemophilic Arthropathy

2020 ◽  
Vol 9 (10) ◽  
pp. 3247
Author(s):  
Jung-Kwon Bae ◽  
Kang-Il Kim ◽  
Sang-Hak Lee ◽  
Myung-Chul Yoo
Keyword(s):  
Total Knee Arthroplasty ◽  
Knee Arthroplasty ◽  
Term Survival ◽  
Long Term Survival ◽  
Hemophilic Arthropathy ◽  
Prosthesis Survival ◽  
Total Knee ◽  
The Mean

While satisfactory results have been reported during short-to mid-term follow-up assessments of hemophilic patients who have undergone total knee arthroplasty (TKA), limited literature focusing on long-term survival following TKA exists to date. As part of this investigation, a consecutive series of 78 TKAs in 56 patients with hemophilic arthropathy was reviewed. The mean patient age at the time of operation was 38.7 years old and the mean length of follow up was 10.2 years. Clinical and radiologic outcomes, quality of life, complications, and long-term survivorship of TKA were evaluated. At the latest point of follow up, the average American Knee Society (AKS) knee and function scores had improved from 32.1 to 85.7 points and 41.5 to 83.3 points, respectively. Moreover, the average range of motion (ROM) was significantly increased from 64.2° preoperatively to 84.2° postoperatively. The physical and mental Short Form-36 results were also significantly improved at the latest point of follow up. Postoperative complications appeared in 12 knees (15.4%). The readmission rate in the 30 days after discharge was 6.4%. Revision TKA was performed in three knees for periprosthetic joint infection (n = 2 knees) and tibial component loosening (n = 1 knee). The Kaplan–Meier 10- and 13-year prosthesis survival rates were 97.1% and 93.2%, respectively. The current study suggests that the mid-to long-term results of TKA in patients with hemophilic arthropathy are favorable, with successful long-term prosthesis survival achievable in most cases.

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