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Simple Summary Treatment results of acute myeloid leukemia (AML) in elderly patients are unsatisfactory. We investigated in an open label randomized phase II study whether addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy would improve outcome in this population. 231 AML patients > 65 years of age were randomly assigned to receive standard chemotherapy with or without tosedostat for two cycles. We found that complete bone marrow leukemia clearance was not significantly different between both arms. After two years, survival was 33% for the standard arm versus 18% for the tosedostat arm. More patients died due to infectious complications in the tosedostat arm than after standard treatment. Also, a cardiac rhythm abnormality called atrial fibrillation was more often seen in the tosedostat arm. We conclude that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly patients with acute myeloid leukemia. Abstract Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation was more common in the tosedostat arm as well. The results of the present study show that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients.

Hairy cell leukemia (HCL) remains an incurable disease. However, first-line treatment with either intravenous or subcutaneous cladribine generally leads to long-lasting remissions. Although there are excellent long-term data for intravenous application, similar data regarding subcutaneous administration are lacking. We therefore analyzed the long-term outcome of 3 prospective multicenter clinical trials on subcutaneous cladribine performed by the Swiss Group for Clinical Cancer Research (SAKK), which recruited 221 patients with classical HCL between 1993 and 2005. Median overall survival from start of treatment was not reached. Pretreatment anemia, higher Eastern Cooperative Oncology Group score, and higher age were associated with poorer overall survival in multivariable analysis, whereas early progression at 24 and 36 months had no significant impact on overall survival. Second-line treatment was necessary in 53 (23.7%) patients after a median of 5 (range, 0.2-20.4) years, and first retreatment was mainly monotherapy with cladribine (66%) or rituximab (15.1%) or a combination of these drugs (15.1%). A total of 44 (19.9%) patients developed second primary malignancies with a median time to occurrence of 5.7 (range, 0.01-17.5) years. Second primary malignancies were the main cause for death (14; 27.5%). Compared with a matched normal Swiss population, the incidence of second primary malignancies was not increased. However, survival of patients with HCL was slightly inferior by comparison (P = .036). In conclusion, the outcome of HCL patients treated with subcutaneous cladribine is excellent, and in most patients, 1 cycle of subcutaneous cladribine is sufficient for long-term disease control.

Leukemia : normal and malignant hemopoiesis 30(6), 1255-1262 (2016). doi:10.1038/leu.2016.20, Published by Nature Publ. Group, Basingstoke

Korrektur zu 10.1038/s41375-020-0826-9

Acute Myeloid Leukaemia (AML) is a rare and heterogeneous haematological malignancy with increasing incidence in the elderly. We performed a population-based, observational analysis of AML cases reported to the Cantonal Cancer Registries in Switzerland. Data was aggregated by the National Institute for Epidemiology and Cancer Registration and stratified for the two time periods 2001-2007 and 2008-2013. Overall, 2351 new AML cases were registered with a stable age-standardised incidence rate (3.0 [95 CI: 2.8-3.2] per 100,000 person-years). This indicates that our observed raise of annual AML cases (+10.9%) is mainly related to demographic ageing and not to an increase of age-specific risks. The fraction of non-classifiable AML cases decreased over time (54.6% to 41.8%) but remained high in elderly patients (65-74yrs: 44%; 75-84yrs: 54.2%, 85+yrs: 59.1%), suggesting less accurate diagnostics and reporting with increasing age. 5yrs relative survival (RS) correlated with AML risk class (favorable: 61.7%-68.4%; adverse risk: 11.4%-21.9%) and age (

Unique characteristics discriminate germ cell tumors (GCTs) from other solid malignancies. Patients are predominantly young men between 15 and 40 years with few comorbidities (if any); tumors are particularly sensitive to platinum-based chemotherapy; and a cure is still possible with salvage approaches in patients with progression after first-line chemotherapy. Curative salvage strategies involve conventional-dose chemotherapy (CDCT) or, alternatively, high-dose chemotherapy with autologous stem cell transplantation (HDCT/ASCT), which—in contrast to virtually all other types of solid tumors—can be highly effective.1, 2, 3, 4, 5, 6, 7, 8, 9, 10

Autologous hematopoietic stem cell transplantation for intravascular large B-cell lymphoma: the European Society for Blood and Marrow Transplantation experience

Objective In 2009, international nutritional societies published practice guidelines on screening and nutritional support for patients undergoing stem cell transplantation. Little is known about how these guidelines are implemented in clinical practice. We performed a nationwide survey with the aim of understanding current practice patterns, differences between clinical practice, and international recommendations as well as barriers to the use of nutritional therapy. Methods We performed a qualitative survey including all centers across Switzerland offering allogeneic (n = 3) or autologous (n = 7) stem cell transplantation. We focused on in-house protocols pertaining to malnutrition screening, indications for nutritional support, types of nutritional therapy available and provided, and recommendations regarding neutropenic diets. Results All centers offering allogeneic, and most of the centers offering autologous transplantation, had a malnutrition screening tool, mainly the nutritional risk score (NRS 2002) method. Only one center does not provide nutritional support. There is wide variation regarding start and stop of nutritional therapy as well as route of delivery, with five centers recommending parenteral nutrition and five centers recommending enteral nutrition as a first step. Although all centers offering allogeneic transplantation, and approximately every other autologous transplant center, used a neutropenic diet, specific recommendations regarding the type of food and food handling showed significant variation. Conclusion This Swiss survey found wide variation in the use of nutritional therapy in patients undergoing stem cell transplantation, with low adherence overall to current practice guidelines. Understanding and reducing barriers to guideline implementation in clinical practice may improve clinical outcomes. Close collaboration of centers will facilitate future research needed to improve current practice and ensure high quality of treatment.

International audience; Treatment with rituximab has improved the outcome for patients with non-Hodgkin's lymphoma. Patients with B-lineage acute lymphoblastic leukemia (ALL) may also have the CD20 antigen, which is targeted by rituximab. Although single-group studies suggest that adding rituximab to chemotherapy could improve the outcome in such patients, this hypothesis has not been tested in a randomized trial. We randomly assigned adults (18 to 59 years of age) with CD20-positive, Philadelphia chromosome (Ph)-negative ALL to receive chemotherapy with or without rituximab, with event-free survival as the primary end point. Rituximab was given during all treatment phases, for a total of 16 to 18 infusions. From May 2006 through April 2014, a total of 209 patients were enrolled: 105 in the rituximab group and 104 in the control group. After a median follow-up of 30 months, event-free survival was longer in the rituximab group than in the control group (hazard ratio, 0.66; 95% confidence interval [CI], 0.45 to 0.98; P=0.04); the estimated 2-year event-free survival rates were 65% (95% CI, 56 to 75) and 52% (95% CI, 43 to 63), respectively. Treatment with rituximab remained associated with longer event-free survival in a multivariate analysis. The overall incidence rate of severe adverse events did not differ significantly between the two groups, but fewer allergic reactions to asparaginase were observed in the rituximab group. Adding rituximab to the ALL chemotherapy protocol improved the outcome for younger adults with CD20-positive, Ph-negative ALL. (Funded by the Regional Clinical Research Office, Paris, and others; ClinicalTrials.gov number, NCT00327678 .)

BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) escalated is the preferred upfront Hodgkin lymphoma (HL) treatment in a number of countries. Upon failure, high-dose chemotherapy with autologous stem cell support (HDT/ASCT) is performed, but its effectiveness has not been verified in this setting. We analyzed all Swiss cases of chemosensitive HL autografted after failure of BEACOPP escalated (n = 22) and compared outcomes with 22 cases of HDT/ASCT following frontline ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) failure. Five-year progression-free survival (PFS) was 76% for ABVD and 42% for BEACOPP escalated (p = 0.029). Two- and 5-year overall survival (OS) was 90% and 71% for ABVD and 72% and 65% for BEACOPP escalated, respectively (p = not significant). Three patients in the ABVD and four in the BEACOPP escalated groups underwent allotransplant for relapse after HDT/ASCT. Grade 3-4 toxicities were comparable in both groups. Three cases of therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/t-AML) were recorded in the BEACOPP escalated group. The acceptable PFS and OS of chemosensitive patients with HL autografted after failure of upfront BEACOPP escalated seem to justify this approach.

et al., The management of multiple myeloma has undergone profound changes over the recent past as a result of advances in our understanding of the disease biology as well as improvements in treatment and supportive care strategies. Notably, recent years have seen a surge in studies incorporating the novel agents thalidomide, bortezomib, and lenalidomide into treatment for different disease stages and across different patient groups. This article presents an update to a previous review of European treatment practices and is based on discussions during an expert meeting that was convened to review novel agent data published or presented at medical meetings until the end of 2011 and to assess their impact on treatment strategies. ©AlphaMed Press.

Introduction: Acute Myeloid Leukaemia (AML) is a rare disease with increasing frequency in the elderly and an emerging impact on health care resources. Trends of classification, incidence, mortality, and survival of AML patients have not yet been reported for Switzerland. Given the demographic ageing, we were mainly interested to investigate whether elderly patients have benefited on a population-based level from the recent changes in AML management. Methods: We performed a population-based, observational analysis of AML cases reported to Cantonal Cancer Registries in Switzerland. Data was aggregated by the National Institute for Epidemiology and Cancer Registration and stratified for the two time-periods 2001-2007/2008-2013. The Swiss Federal Statistics Office provided canton-specific mid-year estimates of the size of the general population and mortality statistics. Data from transplanted patients was provided from the registry of the Swiss Blood Stem Cell Transplant Group . Results: 2'351 new AML cases were registered within the observation time at a median age of 68/67 yrs (range 0-96 yrs). The extrapolated mean annual frequency increased from 275 to 305 AML cases (+10.8%) in the two time periods. In contrast, the age-standardized incidence and mortality rates remained stable (3.0 [95 CI: 2.8-3.2] and 1.9-2.0 [1.8-2.1] per 100'000 person-years, respectively). Incidence was up to 1.4-fold more frequent in males and increased up to 7 fold in patients >75 yrs of age. The fraction of non-classifiable AML cases decreased over time (54.6%/41.8%), but remained high in elderly patients (75-84 yrs: 54.1%, 85+ yrs: 59.1%). As expected, 5-year relative survival (RS) correlated directly with AML risk classes (favorable: 61.7-68.4%, intermediate: 14.9%-27.3%, adverse: 11.4%-20.4%, non-classifiable: 11.4%-14.7%) and inversely with age ( Conclusions: AML incidence remained stable during the observation period, indicating that the 10.8% raise in annual case-frequency is mainly related to population growth and ageing and not to an increase of age-specific risk. AML classification improved over time, but non-classifiable AML cases remained high in elderly patients, suggesting that diagnostics and reporting is less accurate with increasing age. A trend towards improved RS was found in AML patients aged 65-74 yrs and with intermediate as well as adverse risk. These trends were caused by multiple factors and mainly based on the general changes of treatment management of AML patients ≥65 yrs. Survival of elderly AML patients remains dismal. Nevertheless, recent progress in clinical management of elderly AML patients resulted in an emerging improvement of survival on a population-based level in Switzerland. The demographic trend will further increase AML burden and has to be taken into account for structural as well as financial considerations for future health care systems. Disclosures Gregor: AbbVie: Other: Personal Fees; Celgene: Other: Personal Fees, Non-Financial Support; Gilead: Other: Personal Fees; GlaxoSmithKline: Other: Personal Fees; Janssen: Other: Personal Fees, Non-Financial Support; Mundipharma: Other: Personal Fees; Novartis: Other: Personal Fees, Non-Financial Support; Roche: Other: Personal Fees, Non-Financial Support.

Daily administration of 2-chlorodeoxyadenosine (Cladribine, CDA) is a standard treatment for hairy cell leukemia, but may cause severe neutropenia and neutropenic fever. This trial compared toxicity and efficacy of weekly versus daily CDA administration. One hundred patients were randomized to receive standard (CDA 0.14 mg/kg/day day 1-5 [Arm A]) or experimental treatment (CDA 0.14 mg/kg/day once weekly for 5 weeks [Arm B]). The primary endpoint was average leukocyte count within 6 weeks from randomization. Secondary endpoints included response rates, other acute hematotoxicity, acute infection rate, hospital admission, remission duration, event-free, and overall survival. There was no significant difference in average leukocyte count. Response rate (complete + partial remission) at week 10 was 78% (95% confidence interval (CI) 64-88%) in Arm A and 68% (95% CI 54-80%) in Arm B (p = 0.13). Best response rates during follow-up were identical (86%) in both arms. No significant difference was found in the rate of grade 3+4 leukocytopenia (94%vs. 84%), grade 3+4 neutropenia (90%vs. 80%), acute infection (44%vs. 40%), hospitalization (38%vs. 34%), and erythrocyte support (22%vs. 30%) within 10 weeks. Overall, these findings indicate that there are no apparent advantages in toxicity and efficacy by giving CDA weekly rather than daily.

Hairy cell leukemia (HCL) is a B-cell chronic lymphoproliferative disorder that accounts for about 2% of all leukemias. Infiltration by hairy cells is usually present in the bone marrow and spleen,...

The availability of drugs such as thalidomide, bortezomib and lenalidomide changed the landscape in myeloma treatment and has extended the median survival up to 10 years with a substantial improvement in quality of life. This development prompted a Swiss expert panel to re-evaluate the current status and formulate updated clinical recommendations for the diagnosis and treatment of plasma cell myeloma. These recommendations should help clinicians in their decision making to achieve the best outcome based on currently available data.

Cytogenetic and molecular analyses are essential disease-monitoring parameters in chronic myelogenous leukemia (CML) treated with imatinib. However, a bone marrow morphologic response has not been defined. We reviewed bone marrow histology and cytology of 39 imatinib-treated patients with CML over 49 weeks and introduced a morphologic response score. A significant positive correlation with a complete cytogenetic response was shown for absence of dry tap (P = .04) and abnormal megakaryocytes (P0.001), normalization of cellularity (P = .001) and reduction of fibrosis (P = .01), myelopoiesis:erythropoiesis index (P = .001), blast (P = .001) and basophil count (P0.001). The morphologic score integrating these parameters showed an early and late correlation with cytogenetic response. In conclusion, morphologic criteria for complete cytogenetic response in patients with CML treated with imatinib can be defined. Persistent high-level morphologic abnormalities herald early on a high likelihood to fail treatment and call for more intense or alternative therapy.

Rituximab 375 mg/m(2) weekly x 4 has been reported to induce a 60% response rate in patients with relapsed follicular lymphomas (FL). Our aim was to examine the effect of this rituximab schedule on circulating FL cells in an ongoing multicenter study. One hundred fifty-four patients with FL were examined by nested polymerase chain reaction (PCR) at baseline for the presence of t(14;18) translocation-carrying lymphoma cells in bone marrow and/or blood. Sixty-four patients (42%) had PCR-detectable t(14;18)(+) FL cells. Pretreatment characteristics of these 64 patients were as follows: one had stage I, nine had stage II, 14 had stage III, and 40 had stage IV disease. Thirty-five patients had bulky disease (or = 5 cm) and 25 patients had an elevated serum lactate dehydrogenase (LDH) level. Bone marrow was morphologically assessed in 64 patients, and 39 of these patients had an infiltration with FL cells. Blood samples from 51 patients were available for PCR analysis between weeks 8-12 after induction therapy, and 28 of these patients (55%) were PCR negative. Paired blood and bone marrow samples were available for PCR analysis from 39 patients between weeks 8-12 after induction therapy with rituximab. Thirteen of these patients (33%) did not have PCR-detectable cells in blood and bone marrow, while 26 patients (67%) still had circulating t(14;18)(+) cells in either bone marrow (eight patients), blood (one patient), or both (17 patients). PCR negativity in blood and bone marrow in 13 patients was statistically significantly associated with partial or complete response after induction therapy with rituximab (P = 0.006). However, clearance of PCR-detectable t(14;18)(+) cells in bone marrow and/or blood could not be associated with any low tumor burden pretreatment characteristics such as stages I/II, absence of morphological bone marrow infiltration or tumor bulk ofor = 5 cm, and normal serum LDH.

Clinical trials with intravenous cladribine infusions in pretreated patients with Waldenstrom's macroglobulinaemia have shown a response rate of 40%. Our pharmacokinetic studies revealed that the bioavailability of subcutaneous cladribine is complete but that the concentration-time profile is very different from intravenous administration. We designed this phase II multi-institutional trial to study the activity and toxicity of cladribine given as s.c. bolus injections in patients with symptomatic Waldenstrom's macroglobulinaemia. Between May 1993 and October 1995, 25 patients were accrued: male/female 18/7, median age 65 years (range 44-85). All except one patient had been pretreated with more than one regimen (median 2, range 0-10). 18 patients had progressed under previous therapy and six were in relapse. All patients received cladribine for a total dose of 0.5 mg/kg per cycle as s.c. bolus injections divided over 5 d at > or = 4 week intervals, for a maximum of six cycles. All 25 patients were evaluable for toxicity and response. A total of 67 cycles were administered (median 3 cycles, range 1-6). Overall response rate including disease stabilization which had been progressive under previous therapy was 68%. 10 patients (40%, 95% CI 21-61%) achieved a partial remission. Seven responders had been progressive under previous therapy. Maximum responses were reached no later than the third cycle. Median time to treatment failure and remission duration were 4.4 (range 0.5-33) and 8 months (5-29), respectively. Four patients (16%) suffered from infections W.H.O. grade > or = 2 (pneumonia grade 2, Staphylococcus septicaemia grade 3, viral encephalitis and pneumonia, both grade 4 with complete resolution). No other severe adverse events were observed. Cladribine given as s.c. 5 d bolus injections was found to be active in pretreated Waldenstrom's macroglobulinaemia and resulted in durable remissions.

Deletions of sequences centromeric to the p-arm breakpoint have been described in a subset of patients with inv(16) and acute myeloid leukemia (AML) and reported to be associated with a relatively good prognosis. We have investigated 16 p deletions in a cohort of 15 patients with AML and inv(16) or t(16;16) and compared non-deletion and deletion patients in terms of clinical course. Patients were studied by fluorescence in situ hybridization (FISH) using cosmid zit14 as a probe to detect the presence of 16 p deletions in metaphase chromosomes of leukemic cells. While seven patients (47%) revealed no evidence of a deletion, five patients (33%) presented 16 p deletions, thus bringing further support to the relatively frequent occurrence of this event in inv(16) patients. Remarkably, two patients with inv(16) and one patient with t(16;16) showed a mosaicism of deletion and non-deletion metaphases suggesting the presence of two distinct leukemic cell populations. Results let us assume that 16 p deletions are not restricted to inv(16) and may occur subsequently to inv(16) or t(16;16). The presence of a 16 p deletion in a case of inv(16) associated with CBFB-MYH11 transcript type E indicates that deletions are not limited to CBFB-MYH11 transcript type A rearrangements. Survival of deletion patients was compared with that of non-deletion and mosaic ones. No significant differences were observed. The advantage of FISH for enumerative and quantitative assessment of submicroscopic rearrangements of clinical significance is further emphasized.

Haematopoietic stem cell transplantation (HSCT) is a highly specialised procedure used to treat malignancies of the lymphohaematopoietic system as well as some acquired and inherited disorders of the blood. This analysis by the Swiss Blood Stem Cell Transplantation Group, based on data from 2008-2011, describes, treatment rates in Switzerland for specific indications and compares this with data from Germany, France, Italy and the Netherlands, corrected for the size of the population. Differences in transplant rates, in rates for particular indications, and in the use of specific transplant technologies such as use of unrelated donors, use of cord blood or mismatched family donors are described. These data are put in correlation with donor availability from international registries and with number of transplant teams and number of procedures per team all corrected for population size.

Purpose Half the patients with acute myeloid leukemia (AML) who achieve complete remission (CR), ultimately relapse. Residual treatment-surviving leukemia is considered responsible for the outgrowth of AML. In many retrospective studies, detection of minimal residual disease (MRD) has been shown to enable identification of these poor-outcome patients by showing its independent prognostic impact. Most studies focus on molecular markers or analyze data in retrospect. This study establishes the value of immunophenotypically assessed MRD in the context of a multicenter clinical trial in adult AML with sample collection and analysis performed in a few specialized centers. Patients and Methods In adults (younger than age 60 years) with AML enrolled onto the Dutch-Belgian Hemato-Oncology Cooperative Group/Swiss Group for Clinical Cancer Research Acute Myeloid Leukemia 42A study, MRD was evaluated in bone marrow samples in CR (164 after induction cycle 1, 183 after cycle 2, 124 after consolidation therapy). Results After all courses of therapy, low MRD values distinguished patients with relatively favorable outcome from those with high relapse rate and adverse relapse-free and overall survival. In the whole patient group and in the subgroup with intermediate-risk cytogenetics, MRD was an independent prognostic factor. Multivariate analysis after cycle 2, when decisions about consolidation treatment have to be made, confirmed that high MRD values (> 0.1% of WBC) were associated with a higher risk of relapse after adjustment for consolidation treatment time-dependent covariate risk score and early or later CR. Conclusion In future treatment studies, risk stratification should be based not only on risk estimation assessed at diagnosis but also on MRD as a therapy-dependent prognostic factor.

Anhand der unterschiedlichen Immunantwort auf Polio-Lebendimpfstoff oral (Sabin) gegenuber Polio-Totimpfstoff parenteral (Salk) wird die Bedeutung von Mukosa-Immunitat und systemischer Immunitat aufgezeigt. Anhand von Roteln- und Masern-Epidemien wird gezeigt, dass in Geimpften klinisch inapparente Reinfektionen der Mukosa offenbar weit haufiger auftreten konnen als manifeste Erkrankungen. Diese Erkenntnisse erlauben, einen grossen Teil der in Geimpften aufgetretenen Parotitiden in der Schweiz als sekundare Mukosa-Impfversager bei erhaltener systemischer Immunitat zu verstehen. Bedeutung fur die Impfstrategie und Konsequenzen fur die Impfung in der Praxis werden kurz diskutiert.

Purpose: The use of rituximab, a chimeric monoclonal antibody to CD20, has led to significant improvement in the treatment of B-cell non-Hodgkin's lymphoma and mature B-cell ALL. CD20 is expressed in 30 to 50% of adult BCP-ALL patients. Although some single arm studies suggested that adding rituximab to chemotherapy could improve the outcome of these patients, no randomized study has been reported so far. Methods: To evaluate the potential benefit of adding rituximab, we conducted a multicenter randomized trial comparing the pediatric-inspired GRAALL protocol to the same regimen plus rituximab, in patients aged 18-59 years old with newly diagnosed CD20-positive Ph-negative BCP-ALL enrolled in the GRAALL 2005 trial. CD20 positivity was defined as expression of CD20 in more than 20% of leukemia blasts. Rituximab (375 mg/m2) was given during induction (day 1 and 7), salvage reinduction when needed (day 1 and 7), consolidation blocks (6 infusions), late intensification (day 1 and 7) and first year of maintenance (6 infusions) for a total of 16 to 18 infusions. Allogeneic stem cell transplantation (SCT) was offered in first complete remission (CR) to patients with one or more conventional high-risk criteria and a donor. The primary study objective was event-free survival (EFS). A study sample size of 220 patients was estimated in order to detect a 20% gain in EFS at 2 years (two-sided test, power 85%, type 1 error 5%). A sensitivity analysis was performed after censoring patients allografted in first CR at transplant time. This trial was registered at http://www.clinicaltrials.gov as #NCT00327678. Results: From 2005 to 2014, 220 patients from 56 centers were randomized. Eleven patients had non-eligibility criteria (n=5 Ph+ ALL; n=3 CD20-negative ALL; n=1 HIV infection) or withdrew their consent (n=2) and were accordingly excluded from this modified ITT analysis that dealt with 209 patients (105 in the rituximab arm and 104 in the control arm). Median age was 40 years. Both randomization arms were well balanced for pretreatment characteristics including age, ECOG status, WBC, and central nervous system (CNS) involvement (6% of the whole cohort). After induction ± salvage reinduction, CR rate was 92% and 91% in rituximab and control arm, respectively. In patients who reached CR after first induction and were evaluated for Ig/TCR minimal residual disease level (MRD), the rates of patients with MRD Conclusions: In adults with CD20-positive, Ph-negative, BCP-ALL, the addition of rituximab to the pediatric-inspired GRAALL protocol improves EFS; it also prolongs OS when ignoring patient's outcome after transplantation in first CR. Disclosures Off Label Use: Rituximab is not currently approved for this indication.. Chalandon:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees.

The arrival of the novel agents thalidomide, bortezomib, and lenalidomide has significantly changed our approach to the management of multiple myeloma and, importantly, patient outcomes have improved. These agents have been investigated intensively in different treatment settings, providing us with data to make evidence-based decisions regarding the optimal management of patients. This review is an update to a previous summary of European treatment practices that examines new data that have been published or presented at congresses up to the end of 2010 and assesses their impact on treatment practices. © AlphaMed Press., Advisory Board meeting supported by Janssen Pharmaceutical Companies of Johnson and Johnson in Europe, Middle East, and Africa (EMEA). Unrestricted educational grant provided by Janssen Pharmaceutical Companies of Johnson and Johnson in the EMEA to assist with editorial support.

La thrombocytopenie immune primaire (ITP) est une affection auto-immune acquise avec diminution de la survie des plaquettes et perturbation de la production plaquettaire. Il n'existe aucun test clinique simple permettant de prouver la nature auto-immune de l'affection. Pour cette raison, il s'agit presque toujours d'un diagnostic par exclusion d'autres causes. Bien que les plaquettes soient souvent inferieures a 10 x 109/l lors de la presentation initiale, la tendance hemorragique est etonnamment moderee chez la majorite des patients. Le traitement initial fait toujours appel aux corticosteroides, combines a des immunoglobulines intraveineuses et a des transfusions de plaquettes dans les formes compliquees avec hemorragies significatives. Chez l'enfant, la maladie est souvent induite par des infections virales et son evolution est benigne et spontanement regressive dans la majorite des cas. Chez l'adulte, la maladie est plus souvent persistante ou chroniquement recidivante, et le taux de plaquettes se situe souvent a un taux suffisant pour prevenir des hemorragies spontanees. Seule une faible proportion de patients souffre d'une thrombocytopenie severe prolongee accompagnee de saignements reguliers avec risque d'hemorragies potentiellement fatales. C'est probablement ce groupe de patients restreint qui tirera surtout profit des nouvelles options therapeutiques telles que les agonistes du recepteur de la thrombopoietine. A la lumiere de ces nouvelles possibilites, un groupe d'hematologues suisses s'est reuni pour elaborer des directives concernant la prise en charge de l'ITP conformement aux besoins et aux habitudes de notre pays.

The treatment of multiple myeloma has undergone significant changes in the recent past. The arrival of novel agents, especially thalidomide, bortezomib and lenalidomide, has expanded treatment options and patient outcomes are improving significantly. This article summarises the discussions of an expert meeting which was held to debate current treatment practices for multiple myeloma in Switzerland concerning the role of the novel agents and to provide recommendations for their use in different treatment stages based on currently available clinical data. Novel agent combinations for the treatment of newly diagnosed, as well as relapsed multiple myeloma are examined. In addition, the role of novel agents in patients with cytogenetic abnormalities and renal impairment, as well as the management of the most frequent side effects of the novel agents are discussed. The aim of this article is to assist in treatment decisions in daily clinical practice to achieve the best possible outcome for patients with multiple myeloma.

Purpose We report the long-term results of a randomized clinical trial comparing induction therapy with once per week for 4 weeks single-agent rituximab alone versus induction followed by 4 cycles of maintenance therapy every 2 months in patients with follicular lymphoma. Patients and Methods Patients (prior chemotherapy 138; chemotherapy-naive 64) received single-agent rituximab and if nonprogressive, were randomly assigned to no further treatment (observation) or four additional doses of rituximab given at 2-month intervals (prolonged exposure). Results At a median follow-up of 9.5 years and with all living patients having been observed for at least 5 years, the median event-free survival (EFS) was 13 months for the observation and 24 months for the prolonged exposure arm (P < .001). In the observation arm, patients without events at 8 years were 5%, while in the prolonged exposure arm they were 27%. Of previously untreated patients receiving prolonged treatment after responding to rituximab induction, at 8 years 45% were still without event. The only favorable prognostic factor for EFS in a multivariate Cox regression was the prolonged rituximab schedule (hazard ratio, 0.59; 95% CI, 0.39 to 0.88; P = .009), whereas being chemotherapy naive, presenting with stage lower than IV, and showing a VV phenotype at position 158 of the Fc-gamma RIIIA receptor were not of independent prognostic value. No long-term toxicity potentially due to rituximab was observed. Conclusion An important proportion of patients experienced long-term remission after prolonged exposure to rituximab, particularly if they had no prior treatment and responded to rituximab induction.

This review presents an overview of the most recent data using the novel agents thalidomide, bortezomib, and lenalidomide in the treatment of multiple myeloma and summarizes European treatment practices incorporating these novel agents., The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are being challenged and replaced. In the transplant setting, a number of newer induction regimens are now available that have been shown to be superior to the vincristine, doxorubicin, and dexamethasone regimen. Similarly, in the front-line treatment of patients not eligible for transplantation, regimens incorporating novel agents have been found to be superior to the traditional melphalan plus prednisone regimen. Importantly, some of the novel agents appear to be active in patients with high-risk disease, such as adverse cytogenetic features, and certain comorbidities, such as renal impairment. This review presents an overview of the most recent data with these novel agents and summarizes European treatment practices incorporating the novel agents.

Background: So far, only 9 cases of minimal change glomerulonephritis (MCGN) related to chronic lymphocytic leukemia (CLL) have been described. Case Report: Our patient presented with severe nephrotic syndrome. Diagnostic biopsies confirmed MCGN and early-stage BCLL (Binet A). In contrast to previously described cases, kappa monoclonal IgM and cryoglobulins were also detected. The patient was treated with chlorambucil and prednisone. 3 weeks later, renal function and white blood cell (WBC) count were completely normal. Discussion: Although, in most cases, renal disease and CLL present separately, there is evidence for a causal relationship between the two disorders. Although it is widely approved that early-stage CLL should not be treated by medication, the severe nephrotic syndrome in our patient required immediate intervention. So far, there is no standard therapy for MCGN associated with CLL. Our combination therapy resulted in normalization of the nephrotic syndrome and the WBC count. Hence, we emphasize the importance of early recognition of renal symptoms in CLL and propose a successful therapy for nephrotic syndrome in MCGN associated with early-stage B-CLL. Additionally, the pathophysiological and therapeutic aspects of MCGN associated with CLL are retrospectively discussed.

We evaluated the impact of genetic analysis combining cytogenetics and broad molecular screening on leukemia diagnosis according to World Health Organization (WHO) and on genetic risk assignment. A two-step nested multiplex RT-PCR assay was used that allowed the detection of 29 fusion transcripts. A total of 186 patients (104 males (56%), 174 adults (94%), 12 children (6%), 155 AML (83%), 31 ALL (17%)) characterized by morphology and immunophenotyping were included. Of these 186 patients, 120 (65%) had a genetic abnormality. Molecular typing revealed a fusion transcript in 49 (26%) patients and cytogenetic analysis revealed an abnormal karyotype in 119 (64%). A total of 27 (14%) cases were genetically classified as favorable, 107 (58%) intermediate and 52 (28%) unfavorable. For 38 (20%) patients, there was a discrepancy in the genetic risk assignments obtained from broad molecular screening and cytogenetics. Cryptic fusion transcripts in nine (5%) patients changed the genetic risk assignment in four and the WHO classification in four patients. In 34 patients (18%), cytogenetics defined the risk assignment by revealing structural and numerical chromosomal abnormalities not detected by molecular screening. Broad molecular screening and cytogenetics are complementary in the diagnosis and genetic risk assignment of acute leukemia.

Tetrasomy, pentasomy, and hexasomy 8 (polysomy 8) are relatively rare compared to trisomy 8. Here we report on a series of 12 patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or myeloproliferative disorder (MPD) associated with polysomy 8 as detected by conventional cytogenetics and fluorescence in situ hybridization (FISH). In an attempt to better characterize the clinical and hematological profile of this cytogenetic entity, our data were combined with those of 105 published patients. Tetrasomy 8 was the most common presentation of polysomy 8. In 60.7% of patients, polysomy 8 occurred as part of complex changes (16.2% with 11q23 rearrangements). No cryptic MLL rearrangements were found in cases in which polysomy 8 was the only karyotypic change. Our study demonstrates the existence of a polysomy 8 syndrome, which represents a subtype of AML, MDS, and MPD characterized by a high incidence of secondary diseases, myelomonocytic or monocytic involvement in AML and poor overall survival (6 months). Age significantly reduced median survival, but associated cytogenetic abnormalities did not modify it. Cytogenetic results further demonstrate an in vitro preferential growth of the cells with a high level of aneuploidy suggesting a selective advantage for polysomy 8 cells.

The potential benefits of extended rituximab treatment have been investigated in a randomized trial comparing the standard schedule with prolonged treatment in 202 patients with newly diagnosed or refractory/relapsed follicular lymphoma (FL). All patients received standard treatment (rituximab 375 mg/m(2) weekly x 4). In 185 evaluable patients, the overall response rate was 67% in chemotherapy-naive patients and 46% in pretreated cases (P

Contains fulltext : 57434.pdf (Publisher’s version ) (Closed access) To assess the contribution of interphase fluorescence in situ hybridization (I-FISH) toward the detection of recurring unbalanced chromosomal anomalies at diagnosis, a systematic screening of -5/del(5)(q31), -7, and chromosome 8 aneuploidy was performed on 110 patients with acute myelocytic leukemia or high-risk myelodysplastic syndrome. We searched for monosomy 5/del(5q) by one-color I-FISH with a probe specific for the 5q31 region and for -7/8 by dual-color I-FISH with centromeric probes for chromosomes 7 and 8. Discrepancies between conventional cytogenetics (CC) and I-FISH were observed in 8 of the 110 patients (7.3%). For -5/del(5)(q31), a discordance was observed in two patients with complex abnormalities involving chromosome 5. Whereas no discordance was observed for -7, I-FISH detected a trisomy 7 unnoticed by CC in two cases. In six patients, I-FISH revealed a chromosome 8 aneuploidy not detected by CC. Our results illustrate that, when using this specific set of probes, I-FISH is of special interest for the detection of minor clones with chromosome 8 aneuploidy, breakpoint assessment, and sequence identification (markers). Also, to avoid misinterpretations, I-FISH should not be used alone at disease presentation, particularly in cases complex changes that have clearly established prognostic significance.

Background To assess the activity and toxicity of 2-chlorodeoxyadenosine (cladribine, CDA) given by subcutaneous bolus injections to patients with hairy cell leukemia (HCL). Patients and methods Sixty-two eligible patients with classic or prolymphocytic HCL (33 non-pretreated patients, 15 patients with relapse after previous treatment, and 14 patients with progressive disease during a treatment other than CDA) were treated with CDA 0.14 mg/kg/day by subcutaneous bolus injections for five consecutive days. Response status was repeatedly assessed according to the Consensus Resolution criteria. Results Complete and partial remissions were seen in 47 (76%) and 13 (21%) patients, respectively, for a response rate of 97%. All responses were achieved with a single treatment course. Most responses occurred early (i.e. within 10 weeks) after start of CDA therapy, but response quality improved during weeks and even months after treatment completion. The median time to treatment failure for all patients was 38 months. Leukopenia was the main toxicity. Granulocyte nadir (median 0.2 × 109/l) was strongly associated with the incidence of infections (P = 0.0013). Non-specific lymphopenia occurred early after CDA treatment, and normal lymphocytes recovered slowly over several months. No significant associations were found between infections and nadir count of lymphocytes or any lymphocyte subpopulation. No opportunistic infections were observed. Conclusions One course of CDA given by subcutaneous bolus injections is very effective in HCL. The subcutaneous administration is more convenient for patients and care providers, and has a similar toxicity profile to continuous intravenous infusion. The subcutaneous administration of CDA is a substantial improvement and should be offered to every patient with HCL requiring treatment with CDA.

The clinical use of autologous marrow transplantation in acute myeloid leukemia (AML) has been hampered by the inability to collect adequate numbers of cells after remission induction chemotherapy and the notably delayed hematopoietic regeneration following autograft reinfusion. Here we present a study in which the feasibility of mobilizing stem cells was investigated in newly diagnosed AML. Among 96 AML patients, 76 patients (79%) entered complete remission. Mobilization was undertaken with low dose and high dose schedules of G-CSF in 63 patients, and 54 patients (87%) were leukapheresed. A median of 2.0 x 10(6) CD34+ cells/kg (range 0.1-72.0) was obtained in a median of three leukaphereses following a low dose G-CSF schedule (150 microg/m2) during an average of 20 days. Higher dose regimens of G-CSF (450 microg/m2 and 600 microg/m2) given during an average of 11 days resulted in 28 patients in a yield of 3.6 x 10(6) CD34+ cells/kg (range 0-60.3) also obtained following three leukaphereses. The low dose and high dose schedules of G-CSF permitted the collection of 2 x 10(6) CD34-positive cells in 46% and 79% of cases respectively (P = 0.01). Twenty-eight patients were transplanted with a peripheral blood stem cell (PBSC) graft and hemopoietic repopulation was compared with the results of a previous study with autologous bone marrow. Recovery of granulocytes (>0.5 x 10(9)/l, 17 vs 37 days) and platelets (>20 x 10(9)/l; 26 vs 96 days) was significantly faster after peripheral stem cell transplantation compared to autologous bone marrow transplantation. These results demonstrate the feasibility of PBSCT in the majority of cases with AML and the potential advantage of this approach with respect to hemopoietic recovery.

Summary Purpose To study the efficacy and the safety of cladribine (2-chlorodeoxyadenosine, 2-CDA) administered as 24-hour infusions or as subcutaneous bolus injections at two different doses to patients with relapsing or refractory chronic lymphocytic leukaemia (CLL). Patients and methods In this non randomised 2-cohort study, 20 patients with pretreated CLL received cladribine at a dose of 0.7 mg/kg/cycle as continuous i.v. infusions over seven days (group 1) and 35 patients were treated at a reduced dose of 0.5 mg/kg/cycle given as s.c. bolus injections for five days (group 2). After two cycles of four week duration, response was assessed. In the case of progressive disease, therapy was discontinued, otherwise a maximum of four additional cycles were administered until best response. Results A total of 130 cycles were administered (group 1: 41, group 2: 89). Patient characteristics in both groups were comparable. The median dose intensities were 0.172 mg/kg per week and 0.123 mg/kg per week for groups 1 and 2, respectively (P ≤ 0.0001). The overall response rate for all 55 patients was 38% (95% confidence interval (95% CI): 25%–52%), with 5% CR and 33% PR. Response was similar in both patient groups (35% in group 1, 40% in group 2). No association between cladribine dose intensity and response rate was found, and there was no difference between patients relapsing after or refractory to previous therapies (11 of 24 vs. 10 of 31). Median remission duration was six months in both groups. Toxicity, in particular infections (all WHO grades, 34% in group 1 versus 7% in group 2) and myelosuppression (grade 1–4 neutropenia, 72% versus 41% of cladribine cycles) were statistically significantly more frequent in group 1. Conclusion Cladribine is active in heavily pretreated patients with chronic lymphocytic leukaemias. Dose reduction by 29% led to similar response and remission duration, but to a significant decrease of myelotoxicity and risk of infection. Cladribine administered as s.c. bolus injections at 0.5 mg/kg per cycle is safe and this dose level should not be exceeded in this patient population.

PURPOSE The hematopoietic growth factors (HGFs) introduced into induction chemotherapy (CT) of acute myeloid leukemia (AML) might be of benefit to treatment outcome by at least two mechanisms. HGFs given on days simultaneously with CT might sensitize the leukemic cells and enhance their susceptibility to CT. HGFs applied after CT might hasten hematopoietic recovery and reduce morbidity or mortality. MATERIALS AND METHODS We set out to evaluate the use of granulocyte-macrophage colony-stimulating factor (GM-CSF; 5 microg/kg) in a prospective randomized study of factorial design (yes or no GM-CSF during CT, and yes or no GM-CSF after CT) in patients aged 15 to 60 years (mean, 42) with newly diagnosed AML. GM-CSF was applied as follows: during CT only (+/-, n = 64 assessable patients), GM-CSF during and following CT (+/+, n = 66), no GM-CSF (-/-, n = 63), or GM-CSF after CT only (-/+, n = 60). RESULTS The complete response (CR) rate was 77%. At a median follow-up time of 42 months, probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years were 38% and 37% in all patients. CR rates, OS, and DFS did not differ between the treatment groups (intention-to-treat analysis). Neutrophil recovery (1.0 x 10(9)/L) and monocyte recovery were significantly faster in patients who received GM-CSF after CT (26 days v 30 days; neutrophils, P < .001; monocytes, P < .005). Platelet regeneration, transfusion requirements, use of antibiotics, frequency of infections, and duration of hospitalization did not vary as a function of any of the therapeutic GM-CSF modalities. More frequent side effects (eg, fever and fluid retention) were noted in GM-CSF-treated patients predominantly related to the use of GM-CSF during CT. CONCLUSION Priming of AML cells to the cytotoxic effects of CT by the use of GM-CSF during CT or accelerating myeloid recovery by the use of GM-CSF after CT does not significantly improve treatment outcome of young and middle-aged adults with newly diagnosed AML.

Abstract 3098 Background. Upfront treatment for advanced Hodgkin lymphoma (HL) is a matter of debate. The wide difference in progression-free survival (PFS) or freedom from treatment failure observed between the intensified regimen escalated (esc) BEACOPP and other standard intensity schedules - such us ABVD, ABVD hybrids and BEACOPP baseline - is in contrast with a small difference in overall survival (OS) [NEJM 2011;365 :203 and JCO 2009;27 :4548]. This fact suggests that high-dose therapy with autologous stem-cell transplantation (HDT/ASCT) can salvage more patients treated with standard intensity schedules than escBEACOPP treated patients. Methods. In order to better understand this subject we analyzed all Swiss cases of refractory/relapsed HL that received HDT/ASCT after failure of at least 4 cycles of upfront escBEACOPP (4 to 8 cycles), given alone or combined with other regimens (cases, n=22) and compared outcomes with a control group of 33 patients transplanted after failure of upfront ABVD (N=18), ABDV-based combinations (hybrids, N=7), BEACOPP baseline (N=5) or up to 3 cycles of escBEACOPP plus radiotherapy (N=3). The high-dose schedule used before transplant was BEAM for 51/55 patients and CBV in 1 case and 3 controls. Results. Controls and cases were statistically similar in terms of timing of transplant (median year 2006 vs 2007), age at transplant (median 33 vs 28 years), sex (males 64% vs 68%), HL subtype, Ann Arbor stage, international prognostic score, ESR (38 vs 59 mm/1h) and bulky presentation (35% vs 60%), but there were significantly more B-symptoms among escBEACOPP patients (77% vs 23%, p=0.007). Furthermore, chemosensitivity (94% vs 82%), timing of relapse after upfront treatment (0–3 months: 30% vs 22%, 3–12 months: 18% vs 23% and >12 months: 52% vs 55%), median number of CD34+ cells reinfused (4.11 vs 2.99 ×10*6/kg), and need for a second salvage (12% vs 27%) were not significantly different in the two groups. After a median post transplant follow up of 42.5 months, median PFS was 15.4 months for escBEACOPP, and was not reached for control cases (p=0.145). Two-years OS was 84% for controls (95% CI 65%-93%) and 72% for escBEACOPP (95% CI 45%-87%), while 5-years OS was 68% (95% CI 44%-84%) and 65% (95% CI 37%-83%) for controls and cases, respectively. Four of 33 controls (12%) and 3 of 22 (14%) upfront escBEACOPP cases received an allograft for relapsed HL after HDT/ASCT (p=NS). The incidence of severe (grade 3–4) anemia, thrombocytopenia, neutropenia, diarrhea, stomatitis and neutropenic fever was similar in the two groups. Regarding uncommon/unexpected toxicities of HDT/ASCT, one patient in the escBEACOPP group developed grade 4 encephalopathy, whilst in the control group we observed two cases of acute renal failure, one ARDS and one fatal stroke. One patient in the control group was diagnosed with a T-cell lymphoma after transplant (p=NS). Three t-MDS plus one t-AML were recorded among patients in the escBEACOPP group, with no cases of t-AML/t-MDS occurring among those treated with the less intensive approaches (p=0.023). Conclusion. In our series, overall survival of chemosensitive HL patients autografted after failure of either upfront escBEACOPP or standard intensity regimens is encouraging. HDT/ASCT consolidation of chemosensitive patients failing upfront escBEACOPP seems justified. Disclosures: No relevant conflicts of interest to declare.

Therapy of low-grade non-Hodgkin's lymphoma (NHL) with anti-CD20 specific antibodies (Rituximab) has recently been approved for the treatment of follicular and relapsed or refractory NHL in various countries. Rituximab has shown efficacy without concomitant chemotherapy [1-4], suggesting a new therapeutic principle that probably includes apoptosis induction [5, 6]. To our knowledge, little experience and no published information exists on the use of Rituximab in multiple myeloma. We report the case of a patient in whom Rituximab was used as fourth line therapy of multiple myeloma. Rapid acceleration of tumor progression during anti-CD20 therapy was seen, suggesting that Rituximab promoted tumor growth. In April 1997, a 54-year-old white male with sequelae of a poliomyelitic infection in childhood presented with progressive back pain on thoracic level 8/9. Complete work-up revealed an osteolytic fracture of the eighth thoracic vertebrae, osteolytic lesions of ribs, the left humerus and skull. Vertebral biopsy showed infiltration by malignant plasma cells that were mostly CD20-positive (see Figure 1), bone marrow infiltration was < 5%. Immunofixation revealed a monoclonal IgG lambda

Allo-SCT is currently considered the only curative treatment option of patients (pts) with advanced stages of MDS. The CRIANT study tested in pts without an HLA-id. sibling the value of auto-SCT versus one additional course of high dose cytarabine (HDAC). Pts with identified HLA-id. sibling(s) were candidates for allo-SCT. All pts received remission-induction therapy consisting of idarubicin, cytarabine and etoposide (ICE). Pts who reached CR received one consolidation course (cons) with intermediate dose of cytarabine and idarubicin. All pts without a HLA-id. sibling received filgrastim during the recovery phase of 1st cons to mobilize stem cells and were randomized between ASCT and 2nd cons. Between November 1996 and September 2003, 345 pts were registered (69% of them ≤ 55 years of age and 77% with MDS). Reviewed cytogenetic data were available of 295 (86%) and FISH data of 167 pts (48%). Out of 341 evaluable pts 256 have died and the median follow-up was 5.3 years. The median survival was 1.3 years and the 4-year survival rate was 29% (SE=3%). Age (> vs ≤ 55 yrs: HR=1.5, p=0.003) and the IPSS cytogenetic/FISH score (intermediate vs low: HR=1.5, p=0.02; high vs low: HR=3.1, p

The use of intensive antileukemic treatment is less widely accepted in high-risk MDS pts compared to de novo AML, due to the reported inferior results. It is questionable whether the poorer outcome reflects an intrinsic property of the involved stem cell or a higher frequency of poor prognostic factors. The purpose of this analysis is to identify disease-specific prognostic factors for outcome of young (aged 100 (HR=1.67, p=0.02) and donor availability (HR=0.77, p=0.04). Some variables were of prognostic value for OS in only one of the studies: in the CRIANT study number of cytopenias (3 vs 0–2) and AHD >6 months appeared of prognostic importance for OS, wherease FAB subtype M2/M4 and cytogenetics inv(16)/t(8;21) were prognostic in AML-10. Therefore a specific prognostic score for OS was established for each study, AML-10 (based on cytogenetics, PS, FAB, WBC and age) and CRIANT (based on cytogenetics, nr of cytopenias, age, AHD and WBC). The AML-10 study distinguished 5 groups with an estimated 4-year survival rate of 69%, 40%, 45%, 26% and 17%, resp. The prognostic value of this score has been validated on patients treated in the AML-10 study with mitoxantrone instead of idarubicin: the 4-year survival were 76%, 46%, 41%, 33% and 18%, resp. The CRIANT study distinguished 5 groups with a 4-year survival rates of 72%, 44%, 39%, 12% and 0%, resp. In conclusion: the prognostic scores identify a group of 26% AML and 42% MDS pts, with a 4-year survival less than 20%. Apparently current treatment modalities are unsatisfactory for these poor-risk pts and novel treatment strategies should be offered to these pts in the context of clinical trials. Our finding that different variables are of prognostic importance in MDS/sAML and de novo AML pts supports the hypothesis that these are intrinsically different disorders. The CRIANT-derived score is a valuable alternative for the IPSS in intensively treated high-risk MDS pts.