P1031The impact of the duration of atrial fibrillation persistence for arrhythmia free survival in patients undergoing catheter ablation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Furukawa ◽  
T Yamada ◽  
T Morita ◽  
S Tamaki ◽  
M Kawasaki ◽  
...  
Keyword(s):  
Catheter Ablation ◽  
Outcome Data ◽  
Free Survival ◽  
Group 4 ◽  
Kaplan Meier ◽  
Group 3 ◽  
Group 2 ◽  
Af Recurrence ◽  
Group 1

Abstract Background Catheter ablation (CA) for atrial fibrillation (AF) is a curable treatment option. However, AF recurrence after CA remains an important problem. Although the success rate has been improved after catheter ablation (CA) in patients with paroxysmal AF (PAF), outcome data after CA for persistent AF (PeAF) are highly variable. Previous studies showed the PeAF is one of independent predictors for AF recurrence in comparison to PAF. However, there are little information available on the prognostic significance of AF duration after CA for AF. The aim of this study is to evaluate the impact of AF duration on long-term outcomes of AF ablation in patients with PeAF compared with PAF. Methods We enrolled 778 consecutive patients, who were referred our institution between August 2015 and December 2017 for undergoing the first time CA for AF. We divided 5 groups (Group 1; PAF (n=442), Group 2; PeAF duration ≤6 months (n=198), Group 3; PeAF duration of 6 months to 2 years (n=87), Group 4; PeAF duration of 2–5 years (n=30) and Group 5; PeAF duration ≥5 years (n=21)). All patients followed up for at least 1 year. Outcome data on recurrence of AF after ablation were collected. Results There were no significant differences in baseline clinical characteristics before CA among 5 groups, except for the prevalence of congestive heart failure, left atrial diameter and left ventricular ejection fraction. During a mean follow-up period of 511±298 days, 217 patients had AF recurrence. Kaplan-Meier analysis revealed that AF recurrence was significantly higher in group 2 compared to group 1 (31% vs 20%, p=0.002) and in group 4 compared to group 3 (83% vs 30%, p<0.0001). However, AF recurrence was no significantly differences between groups 2 and 3 (31% vs 30%, p=0.76) and between groups 4 and 5 (83% vs 81%, p=0.45). Of 217 patients with AF recurrence, 154 patients had undergone multiple procedures. After last procedures, during a mean follow-up period of 546±279 days, 61 patients had AF recurrence. Kaplan-Meier analysis revealed that AF recurrence was significantly higher in group 2 compared to group 1 (10% vs 3%, P=0.0005) and in group 4 compared with group 3 (35% vs 10%, p=0.0001). However, AF recurrence was no significantly difference between groups 2 and 3 (10% vs 10%, p=0.91) and between groups 4 and 5 (47% vs 35%, p=0.47). AF Free Survival Curve Conclusion Although patients with PeAF within 2 years had significantly higher AF recurrence compared to PAF, AF ablation might still be a good contributor as the first line approach to improve outcomes in patient with PeAF within 2 years.

Predicted final spinal height in patients with adolescent idiopathic scoliosis can be achieved by surgery regardless of maturity status

2018 ◽  
Vol 100-B (10) ◽  
pp. 1372-1376 ◽  
Author(s):  
H. Bao ◽  
Z. Liu ◽  
M. Bao ◽  
Z. Zhu ◽  
P. Yan ◽  
...  
Keyword(s):  
Adolescent Idiopathic Scoliosis ◽  
Idiopathic Scoliosis ◽  
Growth Restriction ◽  
Fusion Surgery ◽  
Group 4 ◽  
Selective Fusion ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Aims The aim of this study was to investigate the impact of maturity status at the time of surgery on final spinal height in patients with an adolescent idiopathic scoliosis (AIS) using the spine-pelvic index (SPI). The SPI is a self-control ratio that is independent of age and maturity status. Patients and Methods The study recruited 152 female patients with a Lenke 1 AIS. The additional inclusion criteria were a thoracic Cobb angle between 45° and 70°, Risser 0 to 1 or 3 to 4 at the time of surgery, and follow-up until 18 years of age or Risser stage 5. The patients were stratified into four groups: Risser 0 to 1 and selective fusion surgery (Group 1), Risser 0 to 1 and non-selective fusion (Group 2), Risser 3 to 4 and selective fusion surgery (Group 3), and Risser 3 to 4 and non-selective fusion (Group 4). The height of spine at follow-up (HOSf) and height of pelvis at follow-up (HOPf) were measured and the predicted HOS (pHOS) was calculated as 2.22 (SPI) × HOPf. One-way analysis of variance (ANOVA) was performed for statistical analysis. Results Of the 152 patients, there were 32 patients in Group 1, 27 patients in Group 2, 48 patients in Group 3, and 45 patients in Group 4. Significantly greater HOSf was observed in Group 3 compared with Group 1 (p = 0.03) and in Group 4 compared with Group 2 (p = 0.02), with similar HOPf (p = 0.75 and p = 0.83, respectively), suggesting that patients who undergo surgery at Risser grade of 0 to 1 have a shorter spinal height at follow-up than those who have surgery at Risser 4 to 5. HOSf was similar to pHOS in both Group 1 and Group 2 (p = 0.62 and p = 0.45, respectively), indicating that undergoing surgery at Risser 0 to 1 does not necessarily affect final spinal height. Conclusion This study shows that fusion surgery at Risser 0 may result in growth restriction unlike fusion surgery at Risser 3 to 4. Despite such growth restriction, AIS patients could reach their predicted or ‘normal’ spinal height after surgery regardless of baseline maturity status due to the longer baseline spinal length in AIS patients and the remaining growth potential at the non-fusion levels. Cite this article: Bone Joint J 2018;100-B:1372–6.

Atypical BCR-ABL Transcripts Chronic Myelogenous Leukemias Show Particular Features, and Their Classical Worse Prognosis Seems Abrogated by Imatinib Mesylate. A Retrospective Analysis of 22 Patients, on the Behalf of the French Intergroup of CML (Fi(ϕ)-LMC Group).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3285-3285
Author(s):  
Franck E. Nicolini ◽  
Nathalie Grardel ◽  
Sandrine Hayette ◽  
Jean-Michel Cayuela ◽  
Agnès Buzyn ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Group 4 ◽  
Blastic Phase ◽  
Group 3 ◽  
Group 2 ◽  
Worse Prognosis ◽  
Group 1

Abstract Chronic Myelogenous Leukemia (CML) originates in the chromosome (Ph1), a reciprocal translocation, corresponding to the BCR-ABL fusion oncogene. A small proportion (1–2%) of CML patients show breakpoints falling outside of the M-BCR gene on chromosome 22, leading to the synthesis of a variety of atypical BCR-ABL transcripts [either shortened: e1a2 (m-BCR), e6a2, e8a2, b2a3 (e13a3), b3a3 (e14a3), or elongated transcripts: e19a2 (m-BCR)] and to the synthesis of different BCR-ABL proteins. In this study, we retrospectively analysed the clinical characteristics and outcomes of cohorts of CML patients harbouring atypical transcripts in and treated with imatinib (IM). Twenty-two patients were analysed: 9 e1a2 [Group 1 (G1)], 4 e6a2 [Group 2 (G2)], 5 e19a2 [Group 3 (G3)], and 4 e8a2 [Group 4 (G4)] BCR-ABL transcripts. Two patients were in myeloid blastic phase at onset (1 in G1 and 1 in G2) and others in chronic phase. Age at diagnosis was significantly younger for e19a2 patients (39.5 years versus 64 for G1, 58.5 for G2, 72 for G3, p=0.005). Female patients were predominant for G1 (5F/3M), but not for other groups. All patients presented a classical Ph1 at karyotyping analysis at diagnosis, but 1 had a -7 (G1), 1 an additional t(11;16) with the Ph1 (G2), 1 a +8 (G3) and 1 a -Y (G3). The majority of patients presented typical CML features at diagnosis, however number of differences could be found: WBC counts were higher for e1a2 and e8a2 patients (74.2 109/l and 62.7 respectively vs 20.9 for G2, and 37.8 for G3, p&lt;0.03). A significant relative monocytosis was present for e1a2 patients (10% vs 4 (G2), 2.5 (G3), 5.5 (G4), p&lt;0.05), and a marked basophilia was present for e6a2 patients vs others (p&lt;0.0008). There was a trend for higher platelet counts in G3 vs others. Hasford and Sokal scores were somewhat comparable in all groups. Median follow-up since diagnosis was 24 months for G1, 10 for G2, 17 for G3 and 31 for G4. Only one patient received interferon for 7 months before IM (G1), all other patients did not receive any other treatment than hydroxyurea before IM. All patients were treated with IM alone initially at 400–600 mg/day. Median duration of IM was 18 months for G1, 9 for G2, 12 for G3, and 30 for G4. At time of analysis 1 pt in G2 and 1 patient in G3 died of progression (blastic phase), and the overall survival (OS) since IM start was better for e19a2 and e8a2 patients, but patients remain very few. However, these OS do not seem different from what has been observed for M-BCR transcripts (IRIS study). In conclusion, atypical BCR-ABL transcripts CMLs show particular diagnosis features, but their poor prognosis reputation seems abrogated by IM.

Does Upfront Therapy with Fludarabine Increase the Risk of Histological Transformation In Patients with Follicular Lymphoma?

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4885-4885
Author(s):  
Sobia Yaqub ◽  
Todd W. Gress ◽  
Oscar Ballester
Keyword(s):  
Follicular Lymphoma ◽  
Relapse Rate ◽  
Group 4 ◽  
Number Of Patients ◽  
Histological Transformation ◽  
Group 3 ◽  
Group 2 ◽  
Time To Relapse ◽  
Group 1

Abstract Abstract 4885 Introduction: Fludarabine has been reported to increase the incidence of relapse and histological transformation in chronic lymphocytic leukemia (Thornton PD, Leukemia research, 2005) and Waldenstrom macroglobulinemia (Leleu X, J Clincal Oncology, 2009). The purpose of our study was to investigate the role of Fludarabine and the risk of transformation and relapse in follicular lymphoma (FL). Patients and Methods: This is a retrospective single institution study. We included 50 patients consecutively diagnosed with FL Grade I and II based on WHO classification of lymphoid malignancies. Grade III patients were excluded from the study. Median follow up is 2.86 years. Patients were grouped according to the initial therapy chosen by their treating physicians: Group 1(n=14) included patients on observation and radiation therapy, Group 2 (n=6) included patients on Fludarabine based regimens, Group 3(n=13) included CVP-R and other rituximab regimens and Group 4(n=17) included R-CHOP. Data collected included time to the onset of biopsy proven transformation, time to relapse, mortality and overall survival. Level of significance was set at <0.05. Results: Median age of the patients was 56.5 and it was not significantly different for the various groups. High risk FLIPI score was seen in 66% of patients treated with Fludarabine regimens as compared to 61% of R-CHOP treated patients. Overall, relapse occurred in 38% patients and transformation occurred in 16% patients during the follow up period. Fludarabine treated patients had the highest relapse rate: 50% (p=0.03). R-CHOP group has lowest relapse rate: 11%. Transformation rate was highest in the Fludarabine group: 33%, as compared to 13% to 17% in other groups (p=0.10). Mortality rate was 7% in group 1, 16% in group 2, 23% for group 3 and 5% in group 4 (p=0.44). Time to relapse/progression in group 1 was 2.9 years; in group 2 was 2.1 years; in group 3 was 2.7 years and in group 4 was 5.8 years. Conclusions: In our study, Fludarabine treated patients appear to be at higher risk for relapse and transformation compared to patients treated with R-CHOP. The differences can not be explained on the basis of known prognostic factors such as age or FLIPI score. The retrospective nature of the study and the small numbers of patients preclude more definitive conclusions. Further research is needed with large number of patients. Disclosures: No relevant conflicts of interest to declare.

The association of PSA levels and survival outcomes in patients with chemotherapy-naïve, castration-resistant prostate cancer (CRPC) who were treated with androgen receptor signaling axis targeting agent (ARAT): A Japanese cohort study.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 315-315
Author(s):  
Tatsuya Shimomura ◽  
Keiichiro Mori ◽  
Toshihiro Yamamoto ◽  
Hajime Onuma ◽  
Hiroyuki Inaba ◽  
...  
Keyword(s):  
Survival Outcome ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Group 4 ◽  
Castration Resistant ◽  
Signaling Axis ◽  
Psa Response ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

315 Background: PSA decline is used as one of the treatment outcome of androgen receptor signaling axis targeting agent (ARAT) in general. However, correlation between PSA decline and survival outcome is not discussed enough. In this study we evaluated how PSA decline influence the survival outcome of ARAT against chemo-naive castration resistant prostate cancer (CRPC). Methods: A total of 200 chemo-naïve CRPC cases treated with ARAT (abiraterone acetate or enzalutamide) were included in this study. We investigated the relationship between PSA response rate and survival outcome (PSA progression free survival (PSA-PFS), Failure free survival (FFS) and overall survival (OS)). Results: PSA response rate correlated with PSA-PFA, TFS and OS significantly (p<0.0001, <0.0001, 0.0009, respectively). And we categorized PSA decline in four groups, group 1: no PSA decline, group 2: 0-50%, group 3: 50%-90%, group 4: over 90%. Median PSA-PFS were 2M (group 1), 4M (group 2), 10M (group 3) and 16M (group 4) (p<0.0001). Median FFS were 3M (group 1), 6M (group 2), 12M (group 3) and 27M (group 4) (p<0.0001). Median OS were 28M (group 1), 36M (group 2), not reached (group 3 and 4) (p=0.0056). In terms of OS, there is a big different between PSA decline <50% and ≥50% in survival curve. And we compare the factors influencing PSA decline ≥50%. PSA and age at initiating ARAT are significant factors predicting PSA decline 50%. Lower PSA and lower age correlated PSA decline ≥50%. Conclusions: PSA decline strongly correlated with PSA-PFS, FFS and OS in this study. It would be a surrogate marker predicting survival outcomes of chemo-naïve CRPC cases treated with ARAT. Further investigation is warranted to confirm these results.

Arthrography in thumb polydactyly with bifurcation at the interphalangeal or metacarpophalangeal joints provides practical information at surgery

2012 ◽  
Vol 38 (3) ◽  
pp. 267-271 ◽  
Author(s):  
K. Iba ◽  
T. Wada ◽  
K. Kanaya ◽  
G. Oki ◽  
T. Yamashita
Keyword(s):  
Average Duration ◽  
Proximal Phalanx ◽  
Type Iv ◽  
Group 4 ◽  
Age At Surgery ◽  
Group 3 ◽  
Group 5 ◽  
Group 2 ◽  
Group 1

We carried out arthrography in 19 thumbs of 18 patients in whom duplication was observed at the interphalangeal (Wassel type II) or metacarpophalangeal (Wassel type IV) joints on radiographs. The average age at surgery was 12.3 months and average duration of post-surgical follow-up was 21.3 months. Based on the arthrographic findings, the types of cartilaginous connections were subdivided into five groups. In group 1, there was a cartilaginous connection at the base of duplicated phalanges. In group 2, there was a cartilaginous connection of the radial digit between the distal and proximal phalanges, or between the proximal phalanx and metacarpal. In group 3, the phalanges separated at a common joint without any cartilaginous connection. In group 4, the radial digit demonstrated fibrous attachment to the capsule without any joint formation. In group 5, each joint was completely separated without any cartilaginous connection. These arthrographic findings could not be detected on radiographs. Different surgical procedures were carried out according to the form of cartilaginous connection.

P1962Impact of Dual Antiplatelet Therapy duration on clinical outcome after stent implantation for coronary bifurcation lesions: results from the Euro Bifurcation Club - P2BiTO - registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Di Serafino ◽  
H Gamra ◽  
P Cirillo ◽  
M Zimarino ◽  
I J Amat-Santos ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Clinical Outcome ◽  
Dual Antiplatelet Therapy ◽  
Coronary Bifurcation ◽  
Kaplan Meier ◽  
Bifurcation Lesions ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background Duration of Dual Antiplatelet Therapy (DAPT) following Acute Coronary Syndromes (ACS) or Stable Coronary Artery Disease (SCAD) treated with coronary stenting is still debated. Although current guidelines consider several “clinical” criteria to decide for short DAPT (<6 months), standard DAPT (12 months) and prolonged DAPT (>12 months), the relationship between DAPT duration, treatment of bifurcations and its impact on clinical outcome has been poorly investigated in real world registries. Purpose We evaluated the impact of DAPT duration on clinical outcomes in consecutive all-comers patients treated with stenting of coronary artery bifurcation lesions included in the Euro Bifurcation Club -P2BiTO - registry. Methods Data on 5036 consecutive patients who underwent PCI on coronary bifurcation at 17 major coronary intervention centres between January 2012 and December 2014 were collected. The primary endpoint of the study was the cumulative occurrence of Major Adverse Cardiac Events (MACCE), defined as a composite of overall-death death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR) and stroke during the follow-up; the secondary endpoints were the single occurrence of any of the above mentioned events. Results Data on DAPT duration was available for 3992 patients (79%). Patients were divided into 3 groups: Group 1) DAPT <6-months (n=720); Group 2) DAPT >6-months but <12-month (n=1602); Group 3) DAPT >12-months (n=1670). Follow up was completed in 3935 (98%) patients with a median of 20 months (C.I.=12–28). At 24 months after the index procedure, MACCE occurred more frequently in the DAPT <6-month group (Group 1) as compared with both Group 2 and 3 (respectively, 102 (14%) versus 154 (10%) and 164 (10%), HR: 0.72 (0.64–0.82), p<0.001). This difference remains after adjustment for clinical and angiographic characteristics (HR: 0.66 (0.58–0.77), p<0.001). On the contrary, no significant difference was found between Group 2 and Group 3 patients. At the Kaplan-Meier analysis (Figure 1), freedom from MACCE survival was significantly lower in patients receiving DAPT for less than 6 months (Log-Rank: 29.5, p<0.001). Figure 1. Kaplan-Meier curves Conclusions In the P2BiTO registry, short DAPT duration of less than 6 months was associated with a significantly higher risk of MACCE compared to longer DAPT in a real-world registry of patients treated for coronary artery bifurcation stenosis.

Optimising prediction of early metastasis-free survival in uveal melanoma using a four-category model incorporating gene expression profile and tumour size

2021 ◽  
pp. bjophthalmol-2020-317714
Author(s):  
Kelsey Andrea Roelofs ◽  
Parampal Grewal ◽  
Steven Lapere ◽  
Matthew Larocque ◽  
Albert Murtha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Information Criteria ◽  
Free Survival ◽  
Group 4 ◽  
Prognostic Groups ◽  
Class 1 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

BackgroundLargest basal diameter (LBD) appears to have independent prognostic value in uveal melanoma (UM).MethodsAll patients undergoing plaque brachytherapy or enucleation for UM involving the choroid and/or ciliary body between 2012 and 2019.ResultsA total of 348 patients with a mean age of 60±14 years were included and followed for a mean of 40±26 months (3.3±2.2 years). On multivariate analysis, LBD >12 mm remained a significant independent predictor of metastasis for both class 1 (HR 21.90; 95% CI 2.69 to 178.02; p=0.004) and class 2 (HR 2.45; 95% CI, 1.03 to 5.83; p=0.04) tumours. Four prognostic groups were created: group 1 (class 1, LBD <12 mm), group 2 (class 1, LBD ≥12 mm), group 3 (class 2, LBD <12 mm) and group 4 (class 2, LBD ≥12 mm). Life tables were used to calculate the 3-year and 5-year metastasis-free survival: group 1 (98 and 98%), group 2 (86 and 86%), group 3 (81 and 62%) and group 4 (54 and 47%). Compared with the reference category (group 1), the Cox proportional hazard model demonstrated a significant worsening of survival for each progressive category (group 2 (HR 21.59; p=0.004), group 3 (HR 47.12, p<0.001), and group 4 (HR 114.24; p<0.001)). In our dataset, the four-category Cox model performed poorer compared with the American Joint Committee on Cancer (AJCC) and gene expression profile (AJCC+GEP) in the Akaike’s information criteria (AIC) (297 vs 291), fit better with the Bayesian information criteria (BIC) (309 vs 313) and performed similarly with the Harrel’s C (0.86 (95% CI 0.80 to 0.91) vs 0.89 (0.84 to 0.94), respectively).ConclusionsCombination of GEP and LBD allows separation of patients into four easy-to-use prognostic groups and was similar to a model combining AJCC stage with GEP.

Abstract 15925: Efficacy and Safety of Pulmonary Vein Isolation in Active Duty Military Members With Atrial Fibrillation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Andrew S Wilson ◽  
Kelvin N Bush
Keyword(s):  
Atrial Fibrillation ◽  
Pulmonary Vein ◽  
Military Personnel ◽  
Active Duty ◽  
Efficacy And Safety ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Af Recurrence ◽  
Group 1

Introduction: The efficacy and safety of pulmonary vein isolation (PVI) for atrial fibrillation (AF) in the active duty (AD) military population has not been previously reported. Hypothesis: We postulate that PVI is an efficacious and safe treatment for young AD service members with AF. Methods: AD military personnel with AF who underwent PVI from 2004 to 2019 were retrospectively analyzed in four age groups (group 1, n=26, 18 to 27 years; group 2, n=38, 28 to 37 years; group 3, n=28, 38 to 49 years; group 4, n=12, ≥50 years). Primary endpoints were (1) PVI procedural efficacy defined as no or rare AF recurrence (<6 episodes) 12 months after last PVI with or without antiarrhythmic drugs (AAD) and (2) procedure-related adverse events and complications. Results: 104 personnel (mean age 35.6+9 years, 84.6% paroxysmal AF, mean LVEF 60.2+6%, 19.2% maintained on AAD after PVI) underwent 142 PVI procedures with a mean follow up of 55.8+47 months. Procedural efficacy was attained in 96.2% of group 1, 78.9% of group 2, 75.0% of group 3, and 66.7% of group 4 (P=0.004, Figure 1). Freedom from AF was reached in 80.3% of group 1, 55.3% of group 2, 46.4% of group 3, 41.7% of group 4 (P=0.02). AADs were maintained in 11.5% of group 1, 21.0% of group 2, 14.3% of group 3, 41.7% of group 4 (P=0.144) and there was no difference in AF recurrence rates between those with AADs and those without (P=0.091). LVEF <50% trended towards being a significant predictor of AF recurrence (OR, 7; 95% CI, 0.75-65; P=0.051). Complications occurred in only 4 (3.8%) cases (pulmonary vein stenosis, cardiac tamponade, arteriovenous fistula) with no complications in the youngest group. Conclusions: This study suggests that PVI is an effective and safe therapy for younger military personnel with AF desiring to decrease their individual AF burden.

Impact of Peripheral Blood Stem Cell Recruitment on Outcome of Single or Double Autologous Hematopoietic stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5221-5221
Author(s):  
Mauricette Michallet ◽  
Quoc-Hung Le ◽  
Anne-Sophie Michallet ◽  
Anne Thiebaut ◽  
Emmanuelle Tavernier ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Light Chains ◽  
Hematopoietic Stem ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Multiple myeloma remains one of the best indication for intensive chemotherapy followed by autologous hematopoietic stem cell transplantation (autoT). Intensive therapy followed by autologous transplantation is superior to conventional chemotherapy and it was demonstrated that two autoT were superior to one except for patients in very good partial response or in complete response after the first autotransplant. Peripheral blood stem cells (PBSC) can be used as well as bone marrow as HSC source with the same efficacy but very few data have been reported regarding PBSC recruitment. The main goal of our work was to study the impact on overall and event-free survival (OS and EFS) of PBSC recruitment using either growth factors (GF) alone (steady state) or chemotherapy followed by GF. Secondly, we performed a multivariate analysis studying influence on OS and EFS of sex, age, lines of therapy, pretransplant status, TBI, PBSC recruitment and number of autoT. We have analyzed 193 PBSC autoT (1 autoT=160, 2 autoT=33) performed for 160 MM patients [81 males and 71 females, mean age: 55 years (39–71)]. At diagnosis, 88 patients presented a MM Ig G (70k and 18l), 28 Ig A (16k and 12l), 3 Ig D (1k and 2l), 21 light chains k and 13 light chains l, 3 non secreting and 4 with plasmocyte leukemias. According to Durie and Salmon classification 75% of patients were in stage III, 15% in stage II and 10% in progressive I. Before transplantation, patients have received 1 line of poly-chemotherapy (n=141), 2 lines (n=15) or 3 lines (n=4) and 154 were evaluated for the response with 11 complete remission, 113 partial remission and 30 stable or evolutive disease just before transplant. As HSC (n=189), patients received PBSC which were recruited by GF alone (n=105) or cyclophosphamide+GF (n= 84). Conditioning (n=189),consisted in melphalan and TBI (n=51), melphalan alone (n=132), melphalan associated to cyclophosphamide or busulfan (n=6). We divided the population into 4 groups : group 1 who received one autoT of PBSC recruited by GF (n=76), group 2 one autoT of PBSC recruited by chemotherapy+GF (n=50), group 3 two autoT of PBSC recruited by GF (n=16) and group 4 two autoT of PBSC recruited by chemotherapy+GF (n=17). The median follow-up (FU) of the 4 groups were different with shorter FU (group 3: 9.9 months, group 4: 13 months) for patients who received tandem autoT because of the recent character of this strategy as compared to a long term follow-up for patients who received only one transplant (group 1: 35months, group 2: 55.3 months). Probabilities of OS and EFS at 2 years were 76% (95%CI 67–87) and 60% (95%CI 49.5–73) for group 1, 77% (95%CI 65–90.5) and 70% (95%CI 57.5–85) for group 2, 87.5% (95%CI 73–100) and 72.9% (95%CI 49–100) for group 3, 100% and 66.7% (95%CI 36–100) for group 4. The difference was not significant because of follow-up differences between the 4 groups and small number of patients in groups 3 and 4. In addition, multivariate analysis did not show any significant influence of the different studied parameters on OS and EFS. Nevertheless, because of these interesting preliminary results, a longer follow-up is warranted for definitive conclusions.

Multi-Center Phase II Study of CAMPATH-1H Dose De-Escalation Prior to Nonmyeloablative HLA-Identical Sibling Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1055-1055
Author(s):  
Ronjon Chakraverty ◽  
Nilusha Manji ◽  
Richard Clark ◽  
Charles Crawley ◽  
Peter Johnson ◽  
...  
Keyword(s):  
Total Dose ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Significant Risk ◽  
Post Transplantation ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Inclusion of CAMPATH-1H as part of a Fludarabine/Melphalan conditioning regimen is effective at preventing GVHD and reducing non-relapse mortality (NRM)following allogeneic stem cell transplantation. However, these benefits are offset by high rates of infection and potentially a loss of graft-versus-tumor effects. When used at a total dose of 100mg, CAMPATH-1H antibody can still be detected at levels in excess of those required to induce ADCC for several weeks. We reasoned that a reduction in the dose of CAMPATH-1H would permit improved immune reconstitution post-transplantation. We report here the analysis of a national, multi-center trial in which the total dose of CAMPATH-1H was reduced step-wise in separate cohorts from 60mg to 20mg prior to HLA-identical sibling transplantation (n=106). Eligibility criteria included patients with haematological malignancies who were aged 18–65, who had a life expectancy >3 months and who were not suitable for standard myeloablative conditioning. Primary endpoints included PK data, chimerism, NRM and incidence of GVHD or infection. The study received IRB approval and all patients gave informed consent. Four total doses of CAMPATH-1H were tested in consecutive cohorts: group 1, 60mg split between d-2 and d-1 (n=26); group 2, 40mg split between d-2 and d-1 (n=27); group 3, 30mg d-1 (n=28); and group 4, 20mg on day -1 (n=25). 97/106 patients recruited to the study are evaluable with a median follow up of 12 months. Median age was 50 (range 19–64). No major differences were identified in patient characteristics between each cohort. 1-year OS and PFS for the whole population was 80.8% and 67.2% respectively. Peak CAMPATH-IH levels (ug/ml) measured by ELISA on day 0 (n=5 each group) were 7.7 ±1.1 in group 1, 4.3 ±0.7 in group 2, 4.9 ±0.8 in group 3 and 2.7± 0.7 in group 4 (p<0.05 groups 1 vs. each group 2–4). By day 28, CAMPATH-1H levels had fallen substantially in all groups, but especially groups 3/4: 1.1 ±0.4 in group1, 0.6 ±0.1 in group 2, 0.1 ±0.06 in group 3 and 0.1 ±0.06 in group 4 (p<0.05 group 1 vs. each group 3 and 4). In groups 3 and 4, 40% of patients had undetectable CAMPATH-1H levels by day 28. Chimerism data was available in 78 patients and of these, 1 patient showed autologous reconstitution, 52 were mixed chimeras and 25 were full chimeras, with no differences between the groups. Day 100 NRM was 4% in group 1, 8% in group 2, 0% in group 3 and 12% in group 4. Grade III-IV GVHD was 0% in group 1, 4% in group 2, 0% in group 3 and 11% in group 4 (p=0.09 group 1 vs. 4). It is noteworthy that 2 patients in group 4 died of complications secondary to grade IV GVHD, although no patients died of this complication in any of the other cohorts. There were no significant differences in the rates of initial CMV reactivation between the groups, or in the rates of CD4 reconstitution. Cumulative incidences of chronic GVHD at 1-year were 55% and 30% in groups 1 and 2, although further follow up is required in later cohorts. We conclude that significant de-escalation of the CAMPATH-1H dose prior to HLA-identical sibling transplantation is feasible without increasing NRM, although reductions below 30mg are associated with a clinically significant risk of severe acute GVHD. Further studies are warranted to determine whether reductions in CAMPATH-1H dosage will translate into improvements in progression-free survival.

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