Pentostatin induces durable remissions in hairy cell leukemia.

1991 ◽  
Vol 9 (2) ◽  
pp. 243-246 ◽  
Author(s):  
P A Cassileth ◽  
B Cheuvart ◽  
A S Spiers ◽  
D P Harrington ◽  
F J Cummings ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Overall Response Rate ◽  
Disease Free Survival ◽  
Maximal Response ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Free Survival ◽  
Disease Free

Fifty patients with hairy cell leukemia were treated with pentostatin (2'-deoxycoformycin; dCF) for a median of 3 months; 32 (64%) patients achieved complete remission (CR), and 10 (20%) patients achieved partial remission (PR), for an overall response rate of 84%. After reaching maximal response, no maintenance therapy was administered. The median duration of follow-up is now 39 months, and only four of 32 patients in CR and two of 10 patients in PR have relapsed. dCF therapy produces durable long-term, disease-free survival in patients with hairy cell leukemia.

scholarly journals Long-term follow-up of patients with hairy cell leukemia after treatment with 2'-deoxycoformycin

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4061-4063 ◽  
Author(s):  
EH Kraut ◽  
MR Grever ◽  
BA Bouroncle
Keyword(s):  
Complete Remission ◽  
Hairy Cell Leukemia ◽  
Disease Free Survival ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Cell Counts ◽  
Long Term Follow Up ◽  
The Impact

Twenty-four patients with advanced hairy cell leukemia treated with 2'- deoxycoformycin (dCF) were studied after achieving complete remission to determine the impact of treatment on survival, disease-free survival, long-term complications of treatment, and response to retreatment. At a median follow-up time of 82 months (range, 54 to 104 months), 23 of 24 patients remain alive. One patient has died of recurrent disease refractory to treatment. Of the remaining 23 patients, 11 have relapsed at a median time of 30 months (range, 7 to 80 months) after treatment completion. Of these 11 patients, 7 have been retreated with dCF or 2'-chlorodeoxyadenosine (2-CdA), including one patient that was retreated twice. All seven patients have responded, with five patients achieving second complete remission. Two patients have had normalization of blood cell counts, but repeat bone marrows have not been performed. No serious infections have been seen in dCF-treated patients during follow-up. One case of Hodgkin's disease and three cases of skin malignancies have developed in these 24 patients. From initiation of treatment, survival is 93 months (range, 63 to 116 months). We concluded that dCF significantly prolongs the survival of patients with advanced hairy cell leukemia without resultant long-term complications. It is too early to predict if this therapy will be curative for the patients still in remission.

scholarly journals 2-chlorodeoxyadenosine induces durable remissions and prolonged suppression of CD4+ lymphocyte counts in patients with hairy cell leukemia

Blood ◽  
1994 ◽  
Vol 83 (10) ◽  
pp. 2906-2911 ◽  
Author(s):  
JF Seymour ◽  
R Kurzrock ◽  
EJ Freireich ◽  
EH Estey
Keyword(s):  
Hairy Cell Leukemia ◽  
Lymphocyte Count ◽  
Disease Free Survival ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Cd4 Lymphocyte Count ◽  
Cd4 Lymphocyte ◽  
Disease Free Survival Rate

Abstract A number of effective treatments are available for patients with hairy cell leukemia (HCL). 2-Chlorodeoxyadenosine (2-CdA) induces more than 80% complete responses, but is associated with profound suppression of CD4+ lymphocyte counts. However, the duration of each is uncertain. We have analyzed a previously reported cohort of 40 patients who had responded to 2-CdA. Eight patients (20%) have relapsed at a median of 16 months (range, 3 to 23 months). The remaining 32 patients were observed for a median of 30 months (range, 7 to 43 months). No patients have died. At 3 years, the actuarial disease-free survival rate is 77% (95% confidence interval, 70% to 84%). The median CD4+ lymphocyte count before therapy was 743/microL (range, 58 to 2,201/microL). The median CD4+ nadir after treatment was 139/microL (range, 25 to 580/microL). There was a single opportunistic infection and no second malignancies observed. Although there was evidence of some improvement in CD4+ lymphocyte counts on sequential testing, CD4+ counts remained significantly lower than baseline (P < .0001) at a median of 23 months after therapy (median, 237/microL; range, 25 to 514/microL), and were also lower than baseline (P < .002) in those patients with more than 1 year of follow-up (median, 27 months; range, 13 to 42 months). The median time to reach an absolute CD4+ lymphocyte count of 365/microL, the lower limit of the normal range, was 40 months. Although responses to 2-CdA are durable in the majority of patients with HCL, the uncertain long-term consequences of the observed CD4+ lymphocytopenia suggest caution in the broad application of this therapy.

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

scholarly journals Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor–Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial

2019 ◽  
Vol 37 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Thomas Ruhstaller ◽  
Anita Giobbie-Hurder ◽  
Marco Colleoni ◽  
Maj-Britt Jensen ◽  
Bent Ejlertsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Contralateral Breast Cancer ◽  
Disease Free Survival ◽  
Luminal Breast Cancer ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Disease Free

Purpose Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. Patients and Methods BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. Results Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. Conclusion Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

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.

Long-Term Follow-Up of Patients With Hairy Cell Leukemia After Cladribine Treatment

Blood ◽  
1998 ◽  
Vol 92 (6) ◽  
pp. 1918-1926 ◽  
Author(s):  
Alan Saven ◽  
Carol Burian ◽  
James A. Koziol ◽  
Lawrence D. Piro
Keyword(s):  
Hairy Cell Leukemia ◽  
Survival Rates ◽  
Complete Response ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Second Neoplasms ◽  
American Society ◽  
La Jolla

Abstract Hairy cell leukemia is a chronic B-cell disorder that follows an indolent, but progressive course. Cladribine (2-chlorodeoxyadenosine) induces complete remissions in the majority of patients after a single course. We report the long-term outcomes, including response rates and their duration; time-to-treatment failure (TTF) rates; retreatment results; toxicities; and survival rates of patients treated at Scripps Clinic (La Jolla, CA). A total of 358 patients with hairy cell leukemia were treated with cladribine at 0.087 or 0.1 mg/kg body weight per day by continuous intravenous infusion for 7 days. The expected number of second neoplasms was based on the National Cancer Institute’s Surveillance Epidemiology and End Results data. Of 349 evaluable patients, 319 (91%) achieved an initial complete response and 22 (7%) a partial response with an overall median duration of response follow-up of 52 months. Ninety patients (26%) had relapsed at a median of 29 months. The TTF rate for all 341 responders was 19% at 48 months, 16% for complete responders, and 54% for partial responders. Of 53 evaluable patients treated with second courses of cladribine at first relapse, 33 (62%) achieved complete responses and 14 (26%) partial responses. Twenty-seven patients (8%) developed second neoplasms (only 1 hematopoietic) with an observed-to-expected ratio of 1.88 (95% confidence interval, 1.24 to 2.74). The overall survival rate was 96% at 48 months. Single courses of cladribine induced long-lasting complete responses in the vast majority of patients. Relapse rates for complete responders were low. Patients who relapse can be successfully retreated with cladribine. Cladribine has high efficacy and a favorable acute and long-term toxicity profile when administered to patients with hairy cell leukemia. © 1998 by The American Society of Hematology.

5-Year Results of Dose-Intensive Sequential Adjuvant Chemotherapy for Women With High-Risk Node-Positive Breast Cancer: A Phase II Study

1999 ◽  
Vol 17 (4) ◽  
pp. 1118-1118 ◽  
Author(s):  
C. Hudis ◽  
M. Fornier ◽  
L. Riccio ◽  
D. Lebwohl ◽  
J. Crown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Pilot Study ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Free Survival ◽  
Dose Dense ◽  
Disease Free

PURPOSE: We conducted a phase II pilot study of dose-intensive adjuvant chemotherapy with doxorubicin followed sequentially by high-dose cyclophosphamide to determine the safety and feasibility of this dose-dense treatment and to estimate the disease-free and overall survival in breast cancer patients with four or more involved axillary lymph nodes. PATIENTS AND METHODS: Seventy-three patients received adjuvant treatment with four cycles of doxorubicin 75 mg/m2 as an intravenous bolus every 21 days, followed by three cycles of cyclophosphamide 3,000 mg/m2 every 14 days with granulocyte colony-stimulating factor support. RESULTS: Seventy-one patients were assessable, and all but two completed all planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. Median disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and overall survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSION: Our pilot study of doxorubicin followed by cyclophosphamide demonstrates the safety and feasibility of the sequential dose-dense plan. Long-term follow-up, although noncomparative, is promising. However, this regimen is associated with a higher incidence of toxicity (and also higher costs) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose-dense approach have been completed but not yet reported. Because the sequential plan can decrease overlapping toxicities, it is an appropriate platform for the addition of newer active agents, such as taxanes or monoclonal antibodies.

Age and Response after Autologous Stem Cell Transplantation (ASCT) Define a Group of Long-Term Event-Free Survivors among Patients (Pts) with Low-Grade Follicular Lymphoma (FL): A Single Institution Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1883-1883
Author(s):  
Charalambos Andreadis ◽  
Elise A. Chong ◽  
Edward A. Stadtmauer ◽  
Selina M. Luger ◽  
David L. Porter ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Autologous Bone Marrow ◽  
Large Cell ◽  
High Dose ◽  
Low Grade ◽  
Free Survival ◽  
Disease Free

Abstract Introduction: FL is generally responsive to conventional-dose chemotherapy but long term disease-free survival (DFS) is uncommon. High-dose chemo-radiotherapy followed by ASCT has the potential to induce remission in this disease but the long-term benefit of this modality remains to be determined. Methods: Between 1990 and 2003, we transplanted 52 pts originally diagnosed with low-grade FL (31 grade 1, 21 grade 2). Twenty-five (48%) had biopsy-proven large cell transformation (FL grade 3 or diffuse large cell lymphoma) before ASCT. The median number of prior therapies was 2 (range: 1 to 7). Prior to ASCT, 45 pts (87%) were responsive to salvage therapy with 20 pts (38%) in CR. Five pts (10%) had chemo-resistant disease at the time of ASCT. High-dose regimens included BCNU-cyclophosphamide-etoposide (31%), melphalan/TBI (27%), and cyclophosphamide/TBI (25%). Thirty-eight pts (73%) received peripheral stem cells (PSCT) and 14 pts (27%) received autologous bone marrow (BM) with 4-hydroxyperoxycyclophosphamide (4-hc) purging in 9 cases (17%). The median age was 49 yrs (range: 29–65). Results: There was 1 treatment-related death during the first 100 days. After ASCT, 36 pts (69%) achieved a CR, 2 (4%) had a PR, and 7 (13%) had stable disease. Among those in CR, 20 (56%) had a CR pre-ASCT, 14 (41%) had a lesser response, and 1 (3%) was chemo-resistant. Median follow-up (f/u) of survivors was 5.3 yrs (range: 1.7 months to 12.4 yrs). The median overall survival (OS) has not yet been reached. The median event-free survival (EFS) is 3.4 yrs (range: 1.7 months to 12.4 yrs). Among complete responders, more than 50% are disease free at last follow-up (range 1.7 months to 12.1 yrs). Variables favorably affecting EFS and OS are age < 60 yrs (p = 0.007, 0.015 respectively), achievement of a CR after ASCT (p = 0.002, 0.001), absence of transformation (p = 0.038, 0.017), BM vs. PSCT (p = 0.042, 0.086), and 4-hc BM purging (p = 0.044, 0.059). Number of prior regimens, response prior to ASCT, type of preparative regimen, and addition of TBI, were not significantly associated with EFS, DFS, or OS. In multivariable analysis, achievement of CR after ASCT and age < 60 yrs are the only significant predictors of EFS and OS. Adjusted for age, 53% of pts with a CR after ASCT are alive and event-free at last f/u (range: 2.4 months to 12.4 yrs) (Figure 1). In contrast, the median EFS among pts without a CR is 0.5 yrs (range: 1.7 months to 5.3 yrs). Conclusion: ASCT is a reasonable therapeutic approach to FL, resulting in long term EFS for some pts, even with relapsed, refractory and/or transformed disease. In our experience, significant predictors of EFS and OS after ASCT are complete response and age <60. The appropriate application and timing of ASCT in the management of pts with FL needs to be further evaluated in randomized, controlled clinical trials. Figure Figure

Pentostatin and Cladribine in Hairy Cell Leukemia- a Retrospective Comparison of a Large Series with Long Follow up.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3472-3472 ◽  
Author(s):  
Monica Else ◽  
Nnenna Osuji ◽  
Ilaria Del ◽  
Estella Matutes ◽  
Rosa Ruchlemer ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Statistical Significance ◽  
Disease Free Survival ◽  
Disease Diagnosis ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Retrospective Comparison ◽  
Significant Difference ◽  
Alternative Agent

Abstract Complete responses (CR) of up to 95% have been reported with both pentostatin and cladribine in patients with hairy cell leukemia (HCL). Although responses are durable, relapses occur even 10 years after treatment. No trial has compared pentostatin to cladribine for HCL. Furthermore, few series achieve sufficient maturity to answer the question: can these agents induce a cure in HCL? We reviewed retrospectively 219 patients with HCL (median follow up (FU) from diagnosis: 12.6 years) to compare pentostatin with cladribine in the treatment of HCL, and to assess the potential for cure in this disease. Diagnosis of HCL and exclusion of HCL-variant were confirmed by central review. Overall response to 1st line pentostatin (n=185) was 96% with CR of 81% and median FU of 10.8 (range 0.3–17.9) years. Response to cladribine was 100% with CR of 82%. No significant difference in response was seen with cladribine (n=34) at median FU of 7.2 (range 0.5–11.5) years. Median disease free survival (DFS) for both agents was 10 years. 38% of patients relapsed 4.9 (range 1–16) years and 4.4 (range 1–10) years after treatment with pentostatin and cladribine, respectively. Although responses were maintained for pentostatin and cladribine when used at 2nd (94% and 100% respectively) and 3rd line (100% and 100% respectively) treatment, CR decreased significantly with each sequential relapse through 70% to 45% (p≤0.01). Attainment of CR at 1st line treatment was significantly associated with increased DFS (p=0.000) as compared to those achieving only partial response (PR). Figure Figure A similar result was seen at 2nd line therapy (p=0.000). DFS also showed a significant decline with sequential treatment (p=0.001) mirroring the reduced likelihood of achieving CR with increasing number of courses. There was some crossover of patients. At 1st relapse, 20 patients received pentostatin of whom 17 had previously received this agent, and 53 patients received cladribine of whom 44 were previously treated with pentostatin. Patients relapsing after an initial CR showed no significant difference in ability to re-attain CR as opposed to PR or no response, whether retreated with the same agent, or switched to the other. However, for patients who initially failed to achieve CR, switching to the alternative agent was associated with an increased rate of CR although this difference did not achieve statistical significance. Known 2nd malignancies (excluding basal cell carcinoma) occurred in 20 patients (9 %). In a separate group of 7 patients who were never treated with either agent, 2 patients developed 2nd malignancies. We demonstrated equivalent efficacies of pentostatin and cladribine in the treatment of HCL. Median survival has not been reached for either agent. At 10 years FU, the survival is 83% (pentostatin) and 90% (cladribine). DFS curves show no plateau for either agent with relapses occurring up to 16 years after pentostatin treatment. True cure in this disease thus remains elusive, however, our results suggest that first line CR with purine analogue therapy should be the prime aim of HCL treatment.

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