Quality of life of patients with chronic lymphocytic leukaemia in the Netherlands: results of a longitudinal multicentre study

Purpose: To describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients. Methods: HRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational study over multiple years. All HRQoL measurements per patient were connected and analysed using area under the curve analysis over the entire study duration. The total patient group was compared with the general population, and three groups of CLL patients were described separately, i.e. patients without any active treatment (“watch and wait”), chlorambucil treatment only, and patients with other treatment(s). Results: HRQoL in the total group of CLL patients was compromised when compared with age- and gender-matched norm scores of the general population. CLL patients scored statistically worse on the VAS and utility score of the EQ-5D, all functioning scales of the EORTC QLQ-C30, and the symptoms of fatigue, dyspnoea, sleeping disturbance, appetite loss, and financial difficulties. In untreated patients, the HRQoL was slightly reduced. In all treatment stages, HRQoL was compromised considerably. Patients treated with chlorambucil only scored worse on the EORTC QLQ-C30 than patients who were treated with other treatments with regard to emotional functioning, cognitive functioning, bruises, uncomfortable stomach, and apathy. Conclusions: CLL patients differ most from the general population on role functioning, fatigue, concerns about future health, and having not enough energy. Once treatment is indicated, HRQoL becomes considerably compromised. This applies to all treatments, including chlorambucil, which is considered to be a mild treatment

Vincristine, doxorubicin and dexamethasone (VAD) administered as rapid intravenous infusion for first-line treatment in untreated multiple myeloma

We examined the feasibility of achieving a rapid response in patients with previously untreated multiple myeloma by administering vincristine 0.4 mR and doxorubicin 9 mg/m2 as a rapid intravenous infusion for 4 d together with intermittent high-dose dexamethasone 40 mg (VAD) for remission induction treatment in patients who were scheduled to receive high-dose therapy. 139 patients (86 male, 53 female; median age 53 years, range 32-65 years; Durie and Salmon stage IIA: 42, IIB: one, IIIA: 89, IIIB: seven) were included in a prospective multicentre study in which VAD was administered as remission induction treatment and was followed by intensified treatment. The response was evaluated according to the criteria of the Eastern Cooperative Oncology Group (ECOG). The results of treatment were evaluable in 134 patients. Five patients died before evaluation. 86 patients (62%) achieved a partial response (PR) and seven patients (5%) achieved a complete response (CR), which equates to a response rate of 67%. The main side-effect was mild neurotoxicity, which was observed in 18% of the patients. Fever or infections were reported in 27% of the patients. VAD administered as an outpatient regimen, based on rapid intravenous infusion, is an effective induction regimen for untreated myeloma with a 67% response rate and acceptable toxicity

Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia

Abstract. BACKGROUND: In order to improve the molecular response rate and prevent resistance to treatment, combination therapy with different dosages of imatinib and cytarabine was studied in newly diagnosed patients with chronic myeloid leukemia in the HOVON-51 study. DESIGN AND METHODS: Having reported feasibility previously, we hereby report the efficacy of escalated imatinib (200 mg, 400 mg, 600 mg or 800 mg) in combination with two cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) days 1 to 7) in 162 patients with chronic myeloid leukemia. RESULTS: With a median follow-up of 55 months, the 5-year cumulative incidences of complete cytogenetic response, major molecular response, and complete molecular response were 89%, 71%, and 53%, respectively. A higher Sokal risk score was invers

Bortezomib Induction and Maintenance Treatment Improves Survival In Patients With Newly Diagnosed Multiple Myeloma: Extended Follow-Up Of The HOVON-65/GMMG-HD4 Trial

Background We investigated if bortezomib during induction and maintenance improves survival in newly diagnosed Multiple Myeloma (MM).\r\n\r\nMethods 827 eligible patients with newly diagnosed symptomatic MM were randomized to receive induction therapy with VAD (vincristine, doxorubicin, dexamethasone; n=414) or PAD (bortezomib, doxorubicin, dexamethasone; n=413) followed by high-dose melphalan (HDM) and autologous stem cell transplant (ASCT). Maintenance consisted of daily thalidomide 50 mg (VAD) or 2-weekly bortezomib 1.3 mg/m2 i.v. (PAD) for 2 years. The primary analysis was progression-free survival (PFS) adjusted for ISS stage. We here report long-term results of this trial ( P. Sonneveld et al., J Clin Oncol 2012;30:2946-2955 ).\r\n\r\nResults The number of eligible patients, patient characteristics and disease characteristics are similar to those reported before. The response rates during protocol treatment have improved slightly since all patients have now completed treatment: CR+nCR 49% vs 35%, VGPR 26% vs 21% and ≥PR 91% vs 83% (PAD vs VAD).\r\n\r\nAfter a median follow-up of 67 months, 111 of patients treated with VAD and 131 of patients treated with PAD were progression-free and alive. Progression-free survival (PFS) defined as time from randomization until progression, relapse or death (censored at date of alloSCT, if applicable), was superior with PAD when adjusted for ISS, (HR=0.78, 95% CI [0.66-0.91], P=.002) and in multivariate analysis (HR=0.76 (95% CI [0.64-0.90], P=.001). For the secondary endpoint overall survival (OS) the PAD arm was superior when adjusted for ISS (HR=0.80, 95% CI [0.65-1.00], P=.047) as well as in multivariate analysis (HR=0.78, 95% CI [0.63-0.97], P=.027). Landmark analysis from start of maintenance for PFS did not show a significant difference between Thalidomide and Bortezomib maintenance, however, for OS the PAD arm was superior (P=.035) (HR=0.71, 95% CI [0.52-0.98]). Subgroup analysis performed on patients with renal failure at presentation (serum creatinine ≥2 mg/dL; 45 VAD, 36 PAD) showed that the PAD arm was significantly superior for PFS (HR=0.44, 95% CI [0.26-0.75], P=.003) and OS (HR=0.38, 95% CI [0.21-0.69],

Dose-finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia.

Contains fulltext : 70504schattenberg.pdf (publisher's version ) (Closed access)The HOVON cooperative study group performed a feasibility study of escalated imatinib and intravenous cytarabine in 165 patients with early chronic-phase chronic myeloid leukemia (CML). Patients received 2 cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) days 1-7) in conjunction with imatinib (200 mg, 400 mg, 600 mg, or 800 mg), according to predefined, successive dose levels. All dose levels proved feasible. Seven dose-limiting toxicities (DLTs) were observed in 302 cycles of chemotherapy, which were caused by streptococcal bacteremia in 5 cases. Intermediate-dose cytarabine (1000 mg/m(2)) prolonged time to neutrophil recovery and platelet recovery compared with a standard dose (200 mg/m(2)). High-dose imatinib (600 mg or 800 mg) extended the time to platelet recovery compared with a standard dose (400 mg). More infectious complications common toxicity criteria (CTC) grade 3 or 4 were observed after intermediate-dose cytarabine compared with a standard-dose of cytarabine. Early response data after combination therapy included a complete cytogenetic response in 48% and a major molecular response in 30% of patients, which increased to 46% major molecular responses at 1 year, including 13% complete molecular responses. We conclude that combination therapy of escalating dosages of imatinib and cytarabine is feasible. This study was registered at www.kankerbestrijding.nl as no. CKTO-2001-03.8 p

Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: A prospective sibling donor versus no-donor comparison

While commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), according to a sibling donor versus no-donor comparison. Eligible patients (433) were entered in 2 consecutive, prospective studies, of whom 288 (67%) were younger than 55 years, in CR1, and eligible to receive consolidation by either an autologous SCT or an allo-SCT. Allo-SCT was performed in 91 of 96 patients with a compatible sibling donor. Cumulative incidences of relapse at 5 years were, respectively, 24 and 55% for patients with a donor versus those without a donor (hazard ratio [HR], 0.37; 0.23-0.60; P < .001). Nonrelapse mortality estimated 16% (± 4) at 5 years after allo-SCT. As a result, disease-free survival (DFS) at 5 years was significantly better in the donor group: 60 versus 42% in the no-donor group (HR: 0.60; 0.41-0.89; P= .01). After risk-group analysis, improved outcome wa