scholarly journals Prospective Long-Term Follow-up after First-Line Subcutaneous Cladribine Treatment in Patients with Hairy Cell Leukemia. a Study of the SAKK (Swiss Group for Clinical Cancer Research)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2875-2875
Author(s):  
Rudolf A. Benz ◽  
Kornelius Arn ◽  
Martin Andres ◽  
Thomas Pabst ◽  
Urban Novak ◽  
...  
Keyword(s):  
Overall Survival ◽  
Secondary Malignancies ◽  
Hairy Cell ◽  
First Line ◽  
Purine Analogues ◽  
Minor Response ◽  
Kaplan Meier ◽  
Long Term Follow Up

Abstract Introduction : Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with a very indolent clinical course and patients may survive for many decades. First-line treatment with purine analogues such as cladribine (Cld) is considered standard of care since it is very efficient and induces profound remissions. However, patients with HCL often relapse after purine analogues and repeated treatment may increase morbidity and mortality. Despite good clinical evidence of long term control of the disease by several mainly single center studies of patients treated with purine analogues, there is only one study analyzing mainly subcutaneous (sc) treated patients based on registry data. We therefore performed a pooled long-term follow-up analysis of our prospective multicenter studies treating patients with sc Cld focusing on survival, secondary malignancy and retreatment. Materials and Methods : The SAKK included patients treated for HCL in 4 studies between 1993 and 2005. Three studies focused on first-line regimens with sc Cld, whereas the fourth protocol focused on the effect of Rituximab monotherapy in patients pretreated with Cld. Classical morphologic, immunohistochemistry and flow cytometry criteria were used as inclusion criteria and response was assessed by established criteria. Treatment algorithms in the 4 studies were as follows: 1) 5 days of Cld 0.14mg/kg sc followed by max 2 cycles of 7 days of Cld 0.1mg/kg sc in case of minor response or no response (SAKK 32/93); 2) Single shot of Cld 0.25mg/kg sc followed by a maximum of 2 cycles of 0.14mg/kg sc for 5 day in case of minor response, no response or relapse (SAKK 32/95); 3) 5 consecutive days of Cld 0.14mg/kg sc versus the same dose in 5 weekly applications (SAKK 32/98); 4) Rituximab 375 mg/m2iv weekly for 4 weeks in relapsed patients (SAKK 31/98). SAKK 32/93 included 63, SAKK 32/95 74 and SAKK 32/98 100 patients. Of the 26 patients registered in 31/98 20 were already in SAKK 32/93, 32/95 and 32/98. Therefore, we also included the treatment information and follow-up data of these 20 patients. All patients were subject to life-long follow-up within the clinical trials. Further information including secondary malignancies and retreatments were obtained by sending out questionnaires to the treating physicians of the study patients. Of the 237 patients 4 patients were in two of the studies and 10 patients have been excluded because of non-classical HCL phenotype. Therefore, a total of 223 patients were included in the analysis. Overall survival and follow-up time were assessed by Kaplan-Meier and reverse Kaplan-Meier method, respectively. Results : The median age of patients at the time of diagnosis was 55 (range 21 to 96) years, 50 patients were female (22.4%) and 173 (77.6%) male. At the time of data analysis, the median follow-up time was 12.1 (95%-CI 10.0 to 14.0) years. A total of 129 (57.8%) patients had the last follow-up information more than two years prior to the data cut-off in May 2016, however, the available information of all patients was used for the sub-analyses including secondary malignancies or retreatment. By the cut-off date, 49 patients have died, 14 (28.6%) due to secondary malignancies and 7 (14.3%) due to HCL progression. Median overall survival from diagnosis was 31.6 (95%-CI 31.6 to 37.8) years. Retreatment was necessary in 53 (23.7%) patients after a mean of 6 (0.2 to 20.4) years and first retreatment was mainly Cld (64%), rituximab (19%) or Cld and rituximab (13%). 21 patients (9.4%) required more than one retreatment with a mean number of 1.57 (range 1 to 5) treatments. A total of 42 (18.8%) patients developed secondary malignancies with an average time to occurrence of 7.1 (range: 0.1 to 17.7) years. The majority of the secondary malignancies were of non-hematological origin (85.9%), most frequently skin cancer (31.0%), followed by prostate cancer (19.0%) and colorectal cancer (16.7%). Six patients (14.4%) developed hematological secondary malignancies with a predominance of B-lymphoid neoplasms. Conclusion : Long-term overall survival in HCL patients treated with sc Cld was excellent and comparable to studies using iv Cld. Despite the long follow-up, sc Cld had a curative potential and relapses requiring re-treatment were observed only in a minority of patients. Secondary malignancies were predominantly non-hematological. These data indicate that patients need to be followed carefully with a special focus on secondary malignancies. Disclosures Chalandon: Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs.

scholarly journals Incidence of response and long-term follow-up in patients with hairy cell leukemia treated with recombinant interferon alfa-2a [see comments]

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 839-845 ◽  
Author(s):  
E Berman ◽  
G Heller ◽  
S Kempin ◽  
T Gee ◽  
LL Tran ◽  
...  
Keyword(s):  
Disease Progression ◽  
Hairy Cell Leukemia ◽  
Interferon Alfa ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Minor Response ◽  
Recombinant Interferon ◽  
Long Term Follow Up

Abstract Thirty-five evaluable patients with hairy cell leukemia (HCL) were treated with recombinant interferon alfa-2a (rIFN-alpha 2a), given at a dose of 3 X 10(6) units (U) intramuscularly (IM) daily for 6 months followed by 3 X 10(6) U IM three times a week for an additional 18 months in a single institution study. All treatment was stopped after 24 months. Sixty-nine percent of patients achieved a partial response, 11% a minor response, and 3% (one patient) had stable disease. Six patients (17%) did not respond to rIFN-alpha 2a. Two patients (6%) achieved a response but later progressed on treatment. A total of 23 patients completed 2 years of treatment and are evaluable for long-term follow-up at a median of 20 months postcompletion of therapy (range 9 to 32 months). Eleven patients (48%) have had progression of their disease at a median of 10 months (range .5 to 25 months) after treatment was discontinued. Statistical analysis of pretreatment patient characteristics did not reveal any factor(s) associated with a high probability of responding to rIFN-alpha 2a; however, analysis of post-treatment variables measured after 2 years of treatment suggested that a low platelet count was associated with a high rate of disease progression. These findings are compared with other published trials using rIFN-alpha 2b, a similar but not identical rIFN preparation. We conclude that while rIFN-alpha 2a has a high overall response incidence, the rate of disease progression after therapy is discontinued approaches 50%, and that a subset of patients can be identified who are at high risk for recurrence after completing 2 years of treatment.

scholarly journals Incidence of response and long-term follow-up in patients with hairy cell leukemia treated with recombinant interferon alfa-2a [see comments]

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 839-845
Author(s):  
E Berman ◽  
G Heller ◽  
S Kempin ◽  
T Gee ◽  
LL Tran ◽  
...  
Keyword(s):  
Disease Progression ◽  
Hairy Cell Leukemia ◽  
Interferon Alfa ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Minor Response ◽  
Recombinant Interferon ◽  
Long Term Follow Up

Thirty-five evaluable patients with hairy cell leukemia (HCL) were treated with recombinant interferon alfa-2a (rIFN-alpha 2a), given at a dose of 3 X 10(6) units (U) intramuscularly (IM) daily for 6 months followed by 3 X 10(6) U IM three times a week for an additional 18 months in a single institution study. All treatment was stopped after 24 months. Sixty-nine percent of patients achieved a partial response, 11% a minor response, and 3% (one patient) had stable disease. Six patients (17%) did not respond to rIFN-alpha 2a. Two patients (6%) achieved a response but later progressed on treatment. A total of 23 patients completed 2 years of treatment and are evaluable for long-term follow-up at a median of 20 months postcompletion of therapy (range 9 to 32 months). Eleven patients (48%) have had progression of their disease at a median of 10 months (range .5 to 25 months) after treatment was discontinued. Statistical analysis of pretreatment patient characteristics did not reveal any factor(s) associated with a high probability of responding to rIFN-alpha 2a; however, analysis of post-treatment variables measured after 2 years of treatment suggested that a low platelet count was associated with a high rate of disease progression. These findings are compared with other published trials using rIFN-alpha 2b, a similar but not identical rIFN preparation. We conclude that while rIFN-alpha 2a has a high overall response incidence, the rate of disease progression after therapy is discontinued approaches 50%, and that a subset of patients can be identified who are at high risk for recurrence after completing 2 years of treatment.

Palifermin For Prevention Of Oral Mucositis Has No Negative Effect On Long-Term Outcome In Patients With Hematological Malignancies Undergoing HSCT - Long-Term Follow-Up To 15 Years

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4631-4631 ◽  
Author(s):  
Patrick J Stiff ◽  
Ricardo Spielberger
Keyword(s):  
Overall Survival ◽  
Oral Mucositis ◽  
Hematological Malignancies ◽  
Progression Free Survival ◽  
Secondary Malignancies ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Negative Effect

Background Palifermin has been shown to reduce the incidence and duration of severe oral mucositis in hematological stem cell transplantation (HSCT) recipients. A follow-up study was performed to rule out a potential long-term safety risk of palifermin use. Objectives to compare long-term disease outcome (overall survival, disease progression and incidence of secondary malignancies) between palifermin and placebo. Methods This is a long-term follow-up study of patients with hematological malignancies undergoing HSCT and treated with palifermin or placebo to prevent oral mucositis. The aim of the study was to detail any potential late complications due to palifermin exposure. Patients were enrolled between 1997-2003 into four randomized, placebo-controlled phase II/III studies conducted at 31 sites in Australia, Europe and the US. The survival outcomes were compared using hazard ratios (HRs) estimated with Cox model including the treatment group, baseline age, disease type (Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, leukemia), ECOG performance status, country and presence of prior radiotherapy as covariates. The incidence of secondary malignancies was compared with chi-squared test. Results A total of 672 patients were randomized to the parent studies (429 palifermin, 243 placebo) and 543 (345, 198) were enrolled to the long-term follow-up. The median follow-up time for subjects alive was 7.9 years (range 0.1-14.9) for palifermin and 8.8 (0.1-14.8) for placebo. No significant differences were seen for either overall survival (HR = 1.01; 95% confidence interval (CI) 0.78-1.31; p=0.921) or progression-free survival (HR=1.04; 95% CI 0.83-1.31; p=0.733). Secondary malignancies were reported by 13% (palifermin) vs. 11% (placebo) of the patients (p=0.477). The most common secondary malignancies were acute myeloid leukemia/myelodysplastic syndrome (5% vs. 5%) and skin cancers (2% vs. 2%). Conclusion The overall survival, progression-free survival, and the incidence of secondary malignancies were comparable between palifermin and placebo in patients undergoing HSCT. After a follow-up of up to 15 years, no negative effect of palifermin on long-term outcomes was observed. Disclosures: No relevant conflicts of interest to declare.

Rituximab and 2-Chlorodeoxyadenosine in Hairy Cell Leukemia as First Line Treatment: A Faster Way to Remission. Report of Five Cases.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4721-4721 ◽  
Author(s):  
Giuliana Farina ◽  
Giulio Giordano ◽  
Stefano Papini ◽  
Bruno Zappacosta ◽  
Arnaldo Carbone ◽  
...  
Keyword(s):  
Median Time ◽  
Remission Rate ◽  
Long Term Results ◽  
Cell Leukaemia ◽  
Hairy Cell ◽  
First Line ◽  
Purine Analogues ◽  
Term Survival

Abstract Background Hairy-Cell leukaemia (HCL) is an uncommon B-cell chronic lymphoproliferative disorder that accounts for about 2% of all leukaemias. Although the disease is generally indolent in its natural course, the majority of patients requires treatment for life-threatening infections due to pancytopenia or symptomatic splenomegaly. Remarkable progresses have been made in the treatment of HCL. Prior to the advent of nucleoside analogues, which are currently the standard initial treatment, interferon and splenectomy were the most effective therapies. Treatment with purine analogs (PNA) such as 2-chlorodeoxyadenosine (2-CdA) is associated with excellent remission rate and long-term survival. Recently, immunotherapeutic approaches which use monoclonal antibodies, like rituximab, have increased the number of therapeutic options for HCL and offer promising salvage strategies for patients who relapse or who are refractory to treatment with purine analogues. Previously rituximab, used in patients relapsing or refractory to CdA and for elimination of MRD after treatment with PNA, showed hematological CR and good MRD eradication. Patients and treatment We analysed, in a retrospective study, five consecutive patients M/F 4/1, 4 with HCL and one with HCLVariant treated at the diagnosis with one rituximab administration at the dose of 375mg/mq and 2CdA at the dose of 0.14 mg/mq/day s.c. for 5 days. Their median age was 70 years (range 41–71). All patients showed splenomegaly and thrombocytopenia (median platelet count was 65000 with range 49000–88000), four of these presented neutropenia (median count was 435/mmc with range 430–800/mmc) and one patient was severely anemic (Hb < 8 g/dl). Results None of the patients had severe therapy-related side effects. Four patients showed febrile cutaneous rash, although received prophyilaxis with acyclovir. The median time of recovery for neutrophil count >1500/mmc was 20 days (range 15–38) for platlets count> 100000/mmc was 21days (12–21), and hemoglobin level> 8g/dl was 31.5 days(27–36). Our median follow up at today was 264 days(range 40–570). At this time all patients are in hematological and morphologic complete remission. Conclusions The use of Rituximab together with 2CDA in first line therapy is safe and feasible. Moreover when Rituximab is used in such setting, median time of recovery in neutrophils and platelets count is significatively shorter than that obtained after therapy with 2CdA alone (8 and 4 weeks respectively). A longer follow-up is needed to evaluate the long-term results of the treatment.

scholarly journals Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Robert J. Kreitman ◽  
◽  
Claire Dearden ◽  
Pier Luigi Zinzani ◽  
Julio Delgado ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Braf Inhibitor ◽  
Nucleoside Analogs ◽  
High Rate ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Long Term Follow Up

Abstract Background Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL). Methods Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days. Results Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported. Conclusions Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy. Trial registration ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711

Atrial fibrillation associated with increased risk of venous thromboembolism

2015 ◽  
Vol 113 (01) ◽  
pp. 185-192 ◽  
Author(s):  
Chun-Cheng Wang ◽  
Cheng-Li Lin ◽  
Guei-Jane Wang ◽  
Chiz-Tzung Chang ◽  
Fung-Chang Sung ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Incidence Rates ◽  
Vein Thrombosis ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Long Term Follow Up ◽  
Deep Vein

SummaryWhether atrial fibrillation (AF) is associated with an increased risk of venous thromboembolism (VTE) remains controversial. From Longitudinal Health Insurance Database 2000 (LHID2000), we identified 11,458 patients newly diagnosed with AF. The comparison group comprised 45,637 patients without AF. Both cohorts were followed up to measure the incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Univariable and multivariable competing-risks regression model and Kaplan-Meier analyses with the use of Aelon-Johansen estimator were used to measure the differences of cumulative incidences of DVT and PE, respectively. The overall incidence rates (per 1,000 person-years) of DVT and PE between the AF group and non-AF groups were 2.69 vs 1.12 (crude hazard ratio [HR] = 1.92; 95 % confidence interval [CI] = 1.54-2.39), 1.55 vs 0.46 (crude HR = 2.68; 95 % CI = 1.97-3.64), respectively. The baseline demographics indicated that the members of the AF group demonstrated a significantly older age and higher proportions of comorbidities than non-AF group. After adjusting for age, sex, and comorbidities, the risks of DVT and PE remained significantly elevated in the AF group compared with the non-AF group (adjusted HR = 1.74; 95 %CI = 1.36-2.24, adjusted HR = 2.18; 95 %CI = 1.51-3.15, respectively). The Kaplan-Meier curve with the use of Aelon-Johansen estimator indicated that the cumulative incidences of DVT and PE were both more significantly elevated in the AF group than in the non-AF group after a long-term follow-up period (p<0.01). In conclusion, the presence of AF is associated with increased risk of VTE after a long-term follow-up period.

scholarly journals Early and Long-Term Follow-Up for Chronic Type B and Type Non-A Non-B Aortic Dissection Using the Frozen Elephant Trunk Technique

2021 ◽  
Vol 8 ◽  
Author(s):  
Congcong Luo ◽  
Ruidong Qi ◽  
Yongliang Zhong ◽  
Suwei Chen ◽  
Hao Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Aortic Dissection ◽  
Type B ◽  
Frozen Elephant Trunk ◽  
Long Term Outcomes ◽  
Chronic Type ◽  
Elephant Trunk ◽  
Long Term Follow Up

Background: This study aimed to evaluate the early and long-term outcomes of a single center using a frozen elephant trunk (FET) procedure for chronic type B or non-A non-B aortic dissection.Methods: From February 2009 to December 2019, 79 patients diagnosed with chronic type B or non-A non-B aortic dissection who underwent the FET procedure were included in the present study. We analyzed operation mortality and early and long-term outcomes, including complications, survival and interventions.Results: The operation mortality rate was 5.1% (4/79). Spinal cord injury occurred in 3.8% (3/79), stroke in 2.5% (2/79), and acute renal failure in 5.1% (4/79). The median follow-up time was 53 months. The overall survival rates were 96.2, 92.3, 88.0, 79.8, and 76.2% at 1/2, 1, 3, 5 and 7 years, respectively. Moreover, 79.3% of patients did not require distal aortic reintervention at 7 years. The overall survival in the subacute group was superior to that in the chronic group (P = 0.047).Conclusion: The FET technique is a safe and feasible approach for treating chronic type B and non-A non-B aortic dissection in patients who have contraindications for primary endovascular aortic repair. The technique combines the advantages of both open surgical repair and endovascular intervention, providing comparable early and long-term follow-up outcomes and freedom from reintervention.

scholarly journals Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up

Blood ◽  
2018 ◽  
Vol 131 (21) ◽  
pp. 2331-2334 ◽  
Author(s):  
Robert J. Kreitman ◽  
Martin S. Tallman ◽  
Tadeusz Robak ◽  
Steven Coutre ◽  
Wyndham H. Wilson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Aspirate ◽  
Phase 1 ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Key Points ◽  
Long Term Follow Up ◽  
Minimal Residual

Key Points Moxetumomab pasudotox eradicated HCL MRD in >50% of CRs, even by the most sensitive measure, bone marrow aspirate flow cytometry. Elimination of MRD was significantly associated with prolonged CR duration.

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