Factors that influence treatment decision-making in elderly DLBCL patients: a case vignette study.

Elderly patients with diffuse large B-cell lymphoma (DLBCL) are frequently not treated with standard immunochemotherapy, and this influences survival negatively. The purpose of this study was to gain more insight into treatment decision-making by hematologists. Case vignettes concerning patients with DLBCL were presented to hematologists in the Netherlands. Patient characteristics (age, comorbidity) differed per case. Respondents were asked in each case if they would treat the patient with curative intent by means of full-dose chemotherapy or chemotherapy with dose reduction or if they would not treat the patient with curative intent. The vast majority of respondents would treat an elderly patient diagnosed with DLBCL without a relevant medical history with full-dose chemotherapy irrespective of age. In the presence of comorbidity, lack of social support, cognitive disorders, and untreated depression dose reductions in advance are frequently applied or patients are not treated with curative intent. This is most pronounced for patients aged older than 80 years. Respondents working in a university hospital more frequently refrain form full-dose chemotherapy with curative intent compared to respondents working in tertiary medical teaching hospitals or general hospitals. Patients without a relevant medical history are generally treated with curative intent irrespective of age. Cognitive disorders, comorbidity, and depression reduce the change of being treated with curative intent. This is most prominent in the eldest patient category.

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.

Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial.

A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).

Autologous stem-cell transplantation in patients with mantle cell lymphoma beyond 65 years of age: a study from the European Group for Blood and Marrow Transplantation (EBMT).

BACKGROUND: Limited experience is available on the feasibility and efficacy of autologous stem-cell transplantation (ASCT) in patients with mantle cell lymphoma (MCL) beyond 65 years. DESIGN AND METHODS: We analysed 712 patients with MCL treated with ASCT from 2000 to 2007 and reported to the European Group for Blood and Marrow Transplantation registry. Patients>65 years were compared with patients<65 years for the end points non-relapse mortality (NRM), relapse incidence, progression-free survival (PFS), and overall survival (OS). RESULTS: Seventy-nine patients were ≥65 years old. Median time from diagnosis to ASCT was longer in the elderly patients (11 versus 9 months, P=0.005); they had more commonly received at least two treatment lines (62.0% versus 47.9%, P=0.02) and were less commonly in first complete remission at ASCT (35.4% versus 51.2%, P=0.002). Median follow-up after ASCT was 19 and 25 months, respectively. NRM was comparable at 3 months (3.8% versus 2.5%) and at 5 years (5.6% versus 5.0%). There were no differences in relapse rate (66% versus 55% at 5 years), PFS (29% versus 40%) and OS (61% versus 67%) between both populations of patients. CONCLUSION: ASCT beyond 65 years of age is feasible in selected patients with MCL and results in similar disease control and survival as in younger patients.

Effect of thalidomide with melphalan and prednisone on health-related quality of life (HRQoL) in elderly patients with newly diagnosed multiple myeloma: a prospective analysis in a randomized trial.

Thalidomide with melphalan/prednisone (MPT) was defined as standard treatment in elderly patients with multiple myeloma (MM) based on five randomized trials. In one of these trials, HOVON49, a prospective health-related quality-of-life (HRQoL) study was initiated in order to assess the impact of thalidomide on QoL. Patients aged >65 years with newly diagnosed MM were randomized to receive melphalan plus prednisone (MP) or MPT, followed by thalidomide maintenance in the MPT arm. Two hundred eighty-four patients were included in this side study (MP, n=149; MPT n=135). HRQoL was assessed with the EORTC Core QoL Questionnaire (QLQ-C30) and the myeloma-specific module (QLQ-MY24) at baseline and at predetermined intervals during treatment. The QLQ-C30 subscales physical function (P=0.044) and constipation (P<0.001) showed an improvement during induction in favour of the MP arm. During thalidomide maintenance, the scores for the QLQ-MY24 paraesthesia became significantly higher in the MPT arm (P<0.001). The QLQ-C30 subscales pain (P=0.12), insomnia (P=0.068), appetite loss (P=0.074) and the QLQ-MY24 item sick (P=0.086) scored marginally better during thalidomide maintenance. The overall QoL-scale QLQ-C30-HRQoL showed a significant time trend towards more favourable mean values during protocol treatment without differences between MP and MPT. For the QLQ-C30 subscales emotional function and future perspectives, difference in favour of the MPT arm from the start of treatment was observed (P=0.018 and P=0.045, respectively) with no significant 'time × arm' interaction, indicating a persistent better patient perspective with MPT treatment. This study shows that the higher frequency of toxicity associated with MPT does not translate into a negative effect on HRQoL and that MPT holds a better patient perspective.

Efficacy of decitabine in the treatment of patients with chronic myelomonocytic leukemia (CMML).

Chronic myelomonocytic leukemia (CMML) characterized by cytopenias, bone marrow and peripheral blood cell dysplasia is notoriously hard to treat. Recent reclassification of CMML as a myelodysplastic/myeloproliferative (MDS/MPS) disease rather than a myelodysplastic syndrome (MDS) by the World Health Organisation (WHO) has led to a review of CMML patients treated with decitabine. Overall response rates (ORR) (complete response [CR]+partial response [PR]) in the subset of patients with CMML in one pivotal phase 3 trial (D-0007) and two phase 2 trials (PCH 95-11, PCH 97-19) decitabine were reviewed. For consistency across trials, all decitabine-treated patients were evaluated using the phase 2 response criteria (CR was defined by normocellular bone marrow with <5% blasts and normal Hgb, WBC, and platelet counts, and PR required 50% decrease in blast count, increases in Hgb by >1.5 mmol/L, WBC count by >1000, and platelet count by >50,000). A total of 31 patients diagnosed with CMML are included in this review. Similar demographics and disease characteristics were observed in all three studies, with an average age of 70.2 years and 71% of patients male. Baseline WBC of >20,000 were observed in 8/28 (29%) patients and baseline bone marrow blasts >5% in 11/28 (39%) patients. All clinical responses were centrally reviewed. The ORR was 25% (14% CR+11% PR). Hematologic improvement was observed in 11% of patients and stable disease in 39% of patients. The decitabine adverse event profile seen in CMML patients was similar to observations in other hematologic patient populations, with myelosuppression and related infectious complications. These data demonstrate encouraging activity for decitabine in CMML, and suggest that studies in other myeloproliferative diseases may be warranted.

Successful management of chronic myeloid leukaemia with leucapheresis during a twin pregnancy.

We present a 36-year-old woman in whom chronic myeloid leukaemia (CML) was diagnosed during a twin pregnancy. Because of hyperleucocytosis, we started leucapheresis also with the goal of gaining time for discussing treatment options. As this strategy was so effective and our patient was reluctant to take medication, we decided to continue this treatment.

Experience with alemtuzumab in treatment of chronic lymphocytic leukaemia in the Netherlands.

BACKGROUND: Alemtuzumab (MabCampath) is a monoclonal antibody against CD52, indicated as third-line treatment of chronic lymphocytic leukaemia (CLL). As most important side effect opportunistic infections are mentioned. It is, however, unknown whether these complications often lead to problems in general patient care in the Netherlands. METHODS: To gain insight into the use and complications of alemtuzumab therapy, the alemtuzumab-treated CLL patients in 15 hospitals in the Netherlands were evaluated by means of a questionnaire. RESULTS: In the period from 31 October 2001 until 17 November 2005, 27 patients with CLL or prolymphocytic leukaemia (PLL), RAI stage I to IV, Binet stage A to C, received 32 treatments with alemtuzumab. The time from diagnosis until start of alemtuzumab treatment was 6 +/- 4.5 years (mean +/- SD ). The treatment lasted 11 +/- 7 weeks. Of the treatments, 41% could be administered for the full 12 weeks. The most frequent adverse events were fever (72%), shivering (47%), fatigue (22%) and dyspnoea (16%). Haematological side effects consisted of leucopenia (75%), thrombocytopenia (44%), and anaemia (13%). Infectious complications occurred in 12 of 32 (38%) treatments: pneumonia (25%; of which one Pneumocystis carini pneumonia and four Aspergillus infections), sepsis (9%; of which one Listeria), herpes zoster (9%), herpes simplex (6%), CMV reactivation (6%), meningitis (3%) and Guillain Barre (3%). The overall response was 53%, with complete remission in 13%, partial remission in 41%, stable disease in 25% and progressive disease in 13%, and lasted for 8.3 +/- 7.3 months. CONCLUSION: Treatment with alemtuzumab is often terminated prematurely, leading to a suboptimal treatment effect. Fear of severe uncontrollable opportunistic infections seems unjustified.

Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma.

The feasibility and efficacy of up-front high-dose sequential chemotherapy followed by autologous stem cell transplantation (ASCT) in previously untreated adults (median age 33 years; range 15-64) with Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or lymphoblastic lymphoma (LyLy), both without central nervous system or extensive bone marrow involvement was investigated in a multicenter phase II study. Treatment consisted of two sequential high-dose chemotherapy induction courses incorporating prednisone, cyclophosphamide, doxorubicin, etoposide and mitoxantrone, without high-dose methotrexate or high-dose cytarabine. Patients with at least PR went on with BEAM and ASCT. Protocol treatment was completed by 23/27 (85%) BL/BLL and 13/15 (87%) LyLy patients. Median treatment duration until BEAM was 70 (range: 50-116) days. No toxic deaths occurred. Response to treatment was complete response (CR) 81% and partial response (PR) 11% for BL/BLL, CR 73% and PR 20% for LyLy. At a median follow-up of 61 months of patients still alive, six BL/BLL and eight LyLy patients have died. The actuarial 5-year overall and event-free survival estimates are 81 and 73% for BL/BLL vs 46 and 40% for LyLy patients. In conclusion, this short up-front high-dose sequential chemotherapy regimen, followed by ASCT is highly effective in adults with BL/BLL with limited bone marrow involvement, but less so in patients with LyLy.

Paraneoplastic cerebellar degeneration preceding the diagnosis of Hodgkin's lymphoma.

Paraneoplastic cerebellar degeneration (PCD) can present as a severe and (sub)acute cerebellar syndrome. PCD can accompany different kinds of neoplasms including small cell lung cancer, adenocarcinoma of the breast and ovary, and Hodgkin's lymphoma. A 34-year-old patient is described with acute dysarthria, gait ataxia and diplopia. Despite extensive laboratory and radiological evaluations in this patient with rapidly deteriorating cerebellar syndrome, the diagnosis of a paraneoplastic syndrome was only made after several months, when an anti-Tr antibody was detected in his serum. The search for Hodgkin's disease as concomitant disorder was then started and resulted in stage II B disease. The patient was successively treated with six courses of etoposide, bleomycin, vinblastine and dexamethasone and radiotherapy, which resulted in a complete remission of the Hodgkin's disease. After starting therapy the cerebellar degeneration stabilised. The pathogenesis of neuronal damage in central nervous system paraneoplastic disorders such as the one we describe is not completely understood. Antitumour therapy is assumed to be the important cornerstone in stabilising the neurological condition. Improvement of the cerebellar syndrome in anti-Tr autoantibody paraneoplastic disease is a rare achievement. Early recognition of the concomitant disorders (anti-Tr autoantibody disease and Hodgkin's lymphoma) is of crucial importance.

Low-dose 5-aza-2'-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients.

PURPOSE: 5-Aza-2'-deoxycytidine (decitabine; DAC) is a DNA hypomethylating agent that has shown a 50% response rate in a small phase II study in elderly patients with high-risk myelodysplastic syndrome. We performed a second, multicenter phase II study in a larger group of patients to confirm our findings and to study the toxicity of DAC. PATIENTS AND METHODS: Between June 1996 and September 1997, 66 patients (median age, 68 years) from seven centers received DAC 45 mg/m(2)/d for 3 days every 6 weeks. For patients in whom a complete response (CR) was reached after two courses, two further cycles were administered as consolidation therapy. In case of a stable disease situation, improvement, or a partial response (PR), a maximum of six cycles was administered. The primary end points were response rate and toxicity. The secondary end points were response duration, survival from the start of therapy, and overall survival. RESULTS: The observed overall response rate was 49%, with a 64% response rate in the patients with an International Prognostic Scoring System (IPSS) high-risk score. The actuarial median response duration was 31 weeks, with a response duration of 39 weeks and 36 weeks for patients who reached a PR or CR, respectively. The actuarial median survival time from the time of diagnosis was 22 months and from the start of therapy was 15 months. For the IPSS high-risk group, the median survival time was 14 months. The median progression-free survival time was 25 weeks. Myelosuppression was rather common, and the treatment-related mortality rate was 7% and was primarily associated with pancytopenia and infection. Significant responses were observed with regard to megakaryopoiesis, with increases in platelet counts having already occurred after one cycle of DAC therapy in the majority of the responding patients. CONCLUSION: We were able to confirm our previous observation that DAC therapy was effective in half of the studied patients with high-risk myelodysplastic syndrome and is especially active in the patients with the worst prognoses. Myelosuppression was the only major adverse effect observed.

An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2'-deoxycytidine (decitabine) in 177 patients.

During the last 10 years, three European phase II studies were performed to investigate the treatment of elderly patients with myelodysplastic syndrome (MDS) with low-dose 5-aza-2'-deoxycytidine (decitabine, DAC). All these European trial data were reviewed on the basis of the International Prognostic Scoring System (IPSS) risk criteria and the response criteria as recently published by an international working group. To investigate the results in a larger cohort of patients and to determine risk factors, all data were pooled with some observations from the PCH 95-06 US phase II study. The response rate in the 177 patients evaluated (median age 70 years) was 49%. The median response duration was 36 weeks, and the median survival was 15 months. Analysis of the data according to sex, age, French-American-British classification, percentage of blasts in the bone marrow, IPSS risk group, lactate dehydrogenase and cytogenetics did not reveal any factor predictive of response. Overall, 69% of patients benefited, including those with stable disease during therapy. Response duration was significantly shorter with increasing risk (according to the IPSS classification). Haemoglobin level and neutrophil count showed an inverse correlation to the IPSS classification. Univariate analysis showed a significantly inferior survival for elderly patients (>75 years of age) and for those with high levels of serum lactate dehydrogenase (LDH) (more than two times the normal values). Patients with high-risk cytogenetic abnormalities according to the IPSS risk criteria showed better overall survival than those with intermediate-risk abnormalities. When analysed according to the IPSS risk classification, high-risk patients had worse survival prospects following decitabine therapy than those with intermediate risk; however, compared to the originally reported IPPS outcomes for high-risk patients, they probably showed better survival. During the treatment period, 18% of the patients progressed towards acute leukaemia. Decitabine showed a rather low toxicity profile in this elderly patient group. In conclusion, low-dose decitabine is an active drug for the treatment of MDS patients, even for those older than 75 years with bad prognostic characteristics.

Quantification of outpatient management and hospitalization of patients with high-risk myelodysplastic syndrome treated with low-dose decitabine.

Intravenous low-dose 5-aza-2'-deoxycytidine (decitabine) in patients with advanced myelodysplastic syndrome (MDS) yields an approximately 50% overall response rate, including 20-25% complete remission. Decitabine-treated MDS patients can be managed as outpatients after completion of a 3-day infusion schedule. In-hospital nights (IHNs), overall survival (OS), and remaining life spent in hospital were evaluated and compared to a matched control group receiving different standard treatments. Between July 1992 and September 2001, 99 high-risk MDS patients, median age 70 years (range 49-86), were treated with low-dose decitabine. Durations of all hospitalizations were recorded. For matched-pair analysis, 44 decitabine-treated patients were matched to 44 MDS patients according to International Prognostic Scoring System classification, period of diagnosis, age, French-American-British classification, and gender. Median number of IHN across all patients was 56 and survival was 481 days, resulting in 84% of remaining life spent at home. In the matched-pair analysis, the median number of IHN was 57 in the decitabine group vs. 50 in the control group. Median survival was 400 vs. 371 days for the decitabine and control groups, respectively. Median number of remaining life spent at home was identical (83% for both groups). Matched patients who received only best supportive care (n=12) had a shorter median survival than the decitabine patients (234 vs. 400 days), and the proportion of remaining life spent at home was slightly greater (82 vs. 77%). Interestingly, matched patients with induction therapy showed comparable IHN, OS, and remaining life spent at home. In conclusion, high-risk MDS patients treated with low-dose decitabine have better survival, and spend comparable time in hospital than patients treated with supportive treatment.

Exclusion of venous thromboembolism: evaluation of D-Dimer PLUS for the quantitative determination of D-dimer.

The objective of this study was to evaluate if D-Dimer PLUS (Dade Behring, USA), a rapid fully automated assay, could be used as an initial screening test in the diagnosis of venous thromboembolism (VTE). Samples from 274 consecutive symptomatic patients with suspected pulmonary embolism (n=229; 79% outpatients, 21% inpatients), deep venous thrombosis (n=37; 84% outpatients, 16% inpatients) or suspected for both complications (n=8) were tested with this D-dimer assay with a Sysmex CA-1500 Coagulation Analyzer. Clinical probability for pulmonary embolism (PE) or deep venous thrombosis (DVT) was staged according to a pretest risk score proposed by Wells. Final diagnosis of PE and/or DVT was established by spiral-computed tomography of the pulmonary arteries or compression ultrasonography, respectively. PE was diagnosed in 13.5% of the patients, whereas DVT was confirmed in 17.7% of the patients. The optimal cut-off value for exclusion of venous thromboembolism was 130 mug/l, and sensitivity, specificity and negative predictive value (NPV) were 95.0% (95% CI: 92.4-97.6), 30.4% (95% CI: 25.0-35.8) and 97.2% (95% CI: 95.2-99.2), respectively. In fact, two patient with PE were missed using D-Dimer PLUS; both cases were outpatients. In conclusion, this assay appears to be safe when implemented in an algorithm based on clinical assessment, D-dimer concentration, and radiological diagnostic techniques to stratify the risk for PE or DVT. However, higher sensitivities and negative predictive values were claimed in the scarce published reports for the D-Dimer PLUS assay than found in this study.

Continuous infusion of low-dose 5-Aza-2'-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome.

There is no standard therapy for elderly patients with high-risk myelodysplastic syndrome (MDS). The treatment options of low-dose Ara-C and haematopoietic growth factors are disappointing in regard to response rate or response duration. We tested the treatment with a 72-h continuous infusion of low-dose 5-Aza-2'-deoxycytidine (DAC) in a group of 29 elderly patients with high-risk MDS. In 15 patients (54%) we observed a response. Eight complete responses were reached, even among patients with bad prognostic cytogenetic findings. The actuarial median survival from the start of the therapy was 46 weeks. The only (and major) toxicity was myelosuppression, leading to a prolonged cytopenic period and thus leading to five toxic deaths (17%) in this high-risk patient group. We conclude that DAC is an effective drug in the treatment of MDS patients and that it probably works via its cytotoxic activity. Myelotoxicity is its major adverse effect.

Continuous infusion of low-dose 5-Aza-2'-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome.

There is no standard therapy for elderly patients with high-risk myelodysplastic syndrome (MDS). The treatment options of low-dose Ara-C and haematopoietic growth factors are disappointing in regard to response rate or response duration. We tested the treatment with a 72-h continuous infusion of low-dose 5-Aza-2'-deoxycytidine (DAC) in a group of 29 elderly patients with high-risk MDS. In 15 patients (54%) we observed a response. Eight complete responses were reached, even among patients with bad prognostic cytogenetic findings. The actuarial median survival from the start of the therapy was 46 weeks. The only (and major) toxicity was myelosuppression, leading to a prolonged cytopenic period and thus leading to five toxic deaths (17%) in this high-risk patient group. We conclude that DAC is an effective drug in the treatment of MDS patients and that it probably works via its cytotoxic activity. Myelotoxicity is its major adverse effect.

A randomized study of granulocyte colony-stimulating factor applied during and after chemotherapy in patients with poor risk myelodysplastic syndromes: a report from the HOVON Cooperative Group. Dutch-Belgian Hemato-Oncology Cooperative Group.

The purpose of this study was to determine the safety and efficacy of filgrastim as an adjunct to induction and consolidation chemotherapy in poor risk patients with myelodysplastic syndrome (MDS). Filgrastim was given both during and after chemotherapy with the objective to accelerate hematopoietic repopulation and enhance the efficacy of chemotherapy. In a prospective randomized multicentre phase II trial, a total of 64 patients with poor risk primary MDS were randomized to receive either granulocyte colony-stimulating factor (G-CSF, filgrastim, AMGEN, Breda, The Netherlands) 5 microg/kg/day subcutaneously or no G-CSF in addition to daunomycin (30 mg/m2/days 1, 2 and 3 intravenous bolus) and cytarabine (200 mg/m2 days 1-7, continuous infusion). The overall complete response rate was 63%: 73% for patients receiving filgrastim as compared to 52% in the standard arm (P = 0.08). Overall survival at 2 years was estimated at 29% for patients assigned to the filgrastim arm and 16% for control patients (P = 0.22). The median time for recovery of granulocytes towards 1.0 x 10(9)/l post-chemotherapy was 23 days in the filgrastim-treated patients vs 35 days in the standard arm (P = 0.015). There were no differences in time of platelet recovery, length of hospital stay, duration of antibiotic use or infectious complications between the two treatment groups. However the earlier recovery of neutrophils in the filgrastim group was associated with a reduced interval of 9 days between the induction and consolidation cycle. In patients with poor risk MDS the use of filgrastim during and after induction therapy results in a significantly reduced neutrophil recovery time. Further study may be warranted to see if the apparent trend of the improved response to chemotherapy in combination with filgrastim can be confirmed in greater number of patients and to assess the effect of the addition of filgrastim on survival.

A randomized phase II study on the effects of 5-Aza-2'-deoxycytidine combined with either amsacrine or idarubicin in patients with relapsed acute leukemia: an EORTC Leukemia Cooperative Group phase II study (06893).

5-Aza-2'-deoxycytidine combined with either amsacrine or idarubicin has been applied in a treatment protocol for patients with a relapse of acute myeloid or lymphocytic leukemia. Sixty-three patients received 5-Aza-2'-deoxycytidine 125 mg/m2 as a 6 h infusion every 12 h for 6 days in combination with either amsacrine 120 mg/m2 as a 1 h infusion on days 6 and 7 (n=30) or idarubicin 12 mg/m2 as a 15 min infusion on days 5, 6 and 7 (n = 33). Twenty-three patients (36.5%) obtained a complete remission (CR); eight of 30 patients treated with amsacrine and 15 of 33 treated with idarubicin. Patients with an interval of more than 1 year between initial diagnosis and start of the protocol achieved CR in 51.4%, compared to 15.4% for patients with an interval of less than 1 year. Patients with normal cytogenetics had a higher CR rate (61%) than those with abnormal cytogenetic findings (15.8%). Digestive tract and hematologic toxicity was prolonged, compared to standard induction schedules. Median disease-free survival was approximately 8 months, with only 20% of patients staying in remission for more than 1 year. 5-Aza-2'-deoxycytidine is a good antileukemic agent with considerable toxicity. Current results merit further investigations in previously untreated leukemia.

The presence of an HLA-identical sibling donor has no impact on outcome of patients with high-risk MDS or secondary AML (sAML) treated with intensive chemotherapy followed by transplantation: results of a prospective study of the EORTC, EBMT, SAKK and GIMEMA Leukemia Groups (EORTC study 06921).

This report used the framework of a large European study to investigate the outcome of patients with and without an HLA-identical sibling donor on an intention-to-treat basis. After a common remission-induction and consolidation course, patients with an HLA-identical sibling donor were scheduled for allogeneic transplantation and patients lacking a donor for autologous transplantation. In all, 159 patients alive at 8 weeks from the start of treatment were included in the present analysis. In total, 52 patients had a donor, 65 patients did not have a donor and in 42 patients the availability of a donor was not assessed. Out of 52 patients, 36 (69%) with a donor underwent allogeneic transplantation (28 in CR1). Out of 65 patients, 33 (49%) received an autograft (27 in CR1). The actuarial survival rates at 4 years were 33.3% (s.e. = 6.7%) for patients with a donor and 39.0% (s.e. = 6.5%) for patients without a donor (P = 0.18). Event-free survival rates were 23.1% (s.e. = 6.2%) and 21.5% (s.e. = 5.3%), respectively (P = 0.66). Correction for alternative donor transplants did not substantially alter the survival of the group without a donor. Also, the survival in the various cytogenetic risk groups was not significantly different when comparing the donor vs the no-donor group. This analysis shows that patients with high-risk myelodysplastic syndrome and secondary acute myeloid leukemia may benefit from both allogeneic and autologous transplantation. We were unable to demonstrate a survival advantage for patients with a donor compared to patients without a donor.