This trial involved 457 patients and sought to assess the value of early intensification with autologous transplantation in patients with poor prognosis histologically aggressive non-Hodgkin lymphoma (NHL) showing a response to initial CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy. Randomization was made at the time of diagnosis with 223 assigned to continuing CHOP and 234 to 3 cycles of CHOP followed by a BEAM (carmustine, etoposide, cytarabine, melphalan) autograft. Analysis was on an intention to treat basis. After the initial three cycles of CHOP 19% of the whole group were in complete response (CR) and 53% in partial remission (PR). At the end of treatment 86% of patients in the CHOP arm had responded with 58% in CR. In the high-dose therapy arm the overall response rate was 83% with 64% in CR (difference between arms not significant). The progression-free survival (PFS) and overall survival at 5 years for the continuing CHOP arm were 38% and 50% respectively, and for the autograft arm were 44% and 50% (differences not significant). Of the patients who attained CR and subsequently relapsed, there were no long-term survivors in the autograft recipients compared to 46% of the continuing CHOP recipients (P = 0.0008). In conclusion, no survival benefit was demonstrated for an early autograft in first response.

INTRODUCTION:Data seem to indicate that young adults with acute lymphoblastic leukemia (ALL) have a better survival when treated with pediatric protocols compared with adult ALL protocols. The purpose of the study was to report the clinical characteristics and outcome of all children and young adults 10-19 years of age diagnosed with ALL in Denmark between 1992 and 2001.MATERIAL:The study includes 99 patients 10-19 years of age with ALL in Denmark during a ten year period found in the complete NOPHO (Nordic Society of Pediatric Hematology and Oncology) registry and through the Danish Cancer Registry and local pathology databases. Data were retrieved by reviewing medical charts of the patients. A total of 61 children (10-14 years) treated on pediatric protocols and 38 young adults (15-19 years) were diagnosed with ALL. Data were reported as of January 1st 2005.RESULTS:There were no difference with respect to the distribution of T-ALL, CNS-leukemia, total white blood count and high risk chromosomal abnormalities between the two groups. There was a statistical significant lower event free survival (p<0.01) and lower overall survival (p<0.01) in young adults compared with 10-14 year-old children (0.38 vs 0.60 and 0.47 vs 0.67). There were more transplant-related deaths in the young adults. Higher treatment intensity in children may be an additional explanatory factor. Children received more prednisone, vincristine and high-dose methotrexate than young adults.CONCLUSION:Young adult patients with ALL might benefit from therapy with pediatric NOPHO ALL protocols.

Risk-adapted lymphoma treatment requires early and accurate assessment of prognosis. This investigation prospectively assessed the value of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) after two cycles of chemotherapy for prediction of progression-free survival (PFS) and overall survival (OS) in Hodgkin lymphoma (HL). Seventy-seven consecutive, newly diagnosed patients underwent FDG-PET at staging, after two and four cycles of chemotherapy, and after completion of chemotherapy. Median follow-up was 23 months. After two cycles of chemotherapy, 61 patients had negative FDG-PET scans and 16 patients had positive scans. Eleven of 16 FDG-PET-positive patients progressed and 2 died. Three of 61 FDG-PET-negative patients progressed; all were alive at latest follow-up. Survival analyses showed strong associations between early FDG-PET after two cycles and PFS (P < .001) and OS (P < .01). For prediction of PFS, interim FDG-PET was as accurate after two cycles as later during treatment and superior to computerized tomography (CT) at all times. In regression analyses, early interim FDG-PET was stronger than established prognostic factors. Other significant prognostic factors were stage and extranodal disease. Early interim FDG-PET is a strong and independent predictor of PFS in HL. A positive early interim FDG-PET is highly predictive of progression in patients with advanced-stage or extranodal disease.

In 1991 we reported the results from a prospective randomised phase 3 trial comparing 7 days continuous infusion of cytosine arabinoside (ara-C) combined with either daunorubicin (DNR) or aclarubicin (ACR) as direct i.v. injection for 3 days as induction chemotherapy (CT) for patients with de novo acute myeloid leukemia (AML) followed by early intensive consolidation CT with two alternating cycles of high-dose ara-C and two cycles of amsacrine plus etoposide, and finally 3 days of daunomycin plus 7 days of ara-C as administered for induction of remission. A total of 174 patients with de novo AML in the age group 17–65 years were included. The patients have now been followed till death or for at least 7 years, and an evaluation of the long-term survival and the risk of developing secondary neoplasms has been made. The overall survival rate 5-years after diagnosis was 23%, and after 10 years 19%. No difference was found between the two treatment regimens in overall survival or disease-free survival (DFS). For the subgroup of 99 patients who achieved complete remission after one or two induction courses, 5- and 10-year survival rates were 35% and 31% respectively, with the highest survival rates in the age group 17–39 years (57% at 5 years) as compared with 27% in patients aged 40–60 years ( P = 0.007). Seven secondary neoplasms were diagnosed simultaneously with or after the diagnosis of AML indicating a standardized incidence ratio (SIR) of 3.41, (95% CI: 1.60–7.26). In three cases the secondary neoplasms were diagnosed simultaneously with the AML diagnosis and were for that reason completely unrelated to the chemotherapy administered for AML, as the psammomatous meningeoma diagnosed after only 8 months. The remaining three neoplasms which developed subsequently did not significantly exceed the expected number, with a SIR = 1.46 (0.47–4.57). Thus, no increased risk of solid tumors causally related to the intensive chemotherapy for de novo AML was observed. However, a generally increased risk of solid tumors in patients diagnosed simultaneously with the AML diagnosis seems likely. Over 20% of the patients were alive and in complete remission 5 years after the AML diagnosis, and they have a high probability of surviving the next 5-year period.

In a Danish population-based non-Hodgkin's lymphoma (NHL) registry (LYFO) representing a population of 2.7 million all new cases of NHL were registered from 1st January 1983 to 31st May 1994. Incidence data of primary malignant tumours of the brain and central nervous system in western Denmark for the period 1971-1990 have been obtained from the Danish Cancer Registry. During the approximate 11-year period 3124 new cases of NHL were registered. Of these, 1152 (37%) were extranodal and 48 were non-AIDS related primary central nervous system lymphomas (PCNSL) accounting for 4.2% of extranodal NHL and 1.5% of all NHL, respectively. The average annual incidence rate of non-AIDS related PCNSL during the period was 1.56 cases per million population (age range: 15-85 yrs, median: 62 yrs, M/F ratio: 1). In a 23-year period there was no trend towards an increasing incidence of non-AIDS related PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary malignant brain tumours. Incidence of primary malignant brain tumours was stable, except for age ranges over 70 years. Histologically, 85% were high grade, centroblastic diffuse (60%) and immunoblastic lymphoma (13%) (Kiel classification). No T-cell lymphomas were detected. Treatment included surgical resection, whole brain irradiation (WBRT) and chemotherapy. Median survival for those receiving either WBRT or WBRT and chemotherapy was eight months and 20 months, respectively (p = 0.78). Overall survival was 53%, 38% and 26% at one, two and five years. Cox-regression analysis identified only one factor having independent impact on survival in performance score > or = 2 (PCNSL p < 0.001, RR = 5.8).

Long‐term follow‐up data are presented on changes in peripheral blood counts and Hb requirements of 11 patients with myelodysplastic syndromes (MDS) during iron chelation treatment with desferrioxamine for up to 60 months. The erythroid marrow activity was indirectly evaluated by repeated determinations of the serum transferrin receptor concentration. The efficacy of iron chelation was evaluated by repeated quantitative determination of the liver iron concentration by magnetic resonance imaging.Reduction in the Hb requirement (≥50%) was seen in 7/11 (64%) patients. Five patients (46%) became blood transfusion independent. Platelet counts increased in 7/11 (64%) patients and the neutrophil counts in 7/9 (78%) evaluable patients. All patients in whom iron chelation was highly effective showed improvement of erythropoietic output accompanied by an increase in the serum transferrin receptor concentration.It is concluded that reduction in cytopenia in MDS patients may be accomplished by treatment with desferrioxamine, if the iron chelation is efficient and the patients are treated for a sufficiently long period of time. Exactly how treatment with desferrioxamine works remains a challenge for further investigation.

Relapses after autologous transplantation are a serious clinical problem in patients with haematological diseases. The decision making for handling of such patients is difficult and the aim of this retrospective analysis of posttransplant relapses was 1) to obtain information of practical importance for the management of future relapses and 2) to evaluate the basis for clinical phase I-II trials of salvage therapy combined with biological modifiers. Included in the study were 283 patients with acute leukemia, multiple myeloma and malignant lymphoma who relapsed after autologous transplantations during a five year period from 1989 to 1994. Chemo- and radiotherapy was given to 229 patients after relapse or due to progressive disease and the response evaluated after 90 days. Fifty four patients (24%) obtained a complete remission and 44 patients (19%) partial responses. The overall median survival from relapse was 5 months. In the group given salvage treatment the median survival was 7 months and in the 54 patients who obtained remission the median survival was 15 months. So far 6 of 14 patients in continuous complete remission have a remission time after relapse longer than the time in remission after transplantation. Survival after relapse depended upon the time from transplantation to relapse, primary disease and if salvage therapy was given. In conclusion posttransplant relapses can be treated but the strategy has to be evaluated in future clinical trials.

It has been claimed that Primary Central Nervous System Lymphomas (PCNSL), a rare neoplasm accounting for only a small fraction of malignant brain tumors and extranodal non-Hodgkin lymphomas (NHL), occur with increasing frequency in immunologically normal as well as in immunocompromised individuals. In an attempt to characterize the clinicopathological features, outcome and prognostic factors of PCNSL we here report our experience in a large unselected series of patients from a well-defined region. In addition, we present data on trends in incidence of PCNSL and primary malignant brain tumors in a well-defined geographical area. In a Danish population-based NHL registry (LYFO) representing a population of 2.7 million all new cases of NHL were registered during the approximate 11-year period from 1st January 1983 to 31st May 1994. Incidence data of primary malignant tumors of the brain and central nervous system in western Denmark for the period 1971-1990 have been obtained from the Danish Cancer Registry. During the approximate 11-year period 3124 new cases of NHL were registered. Of these, 1152 (37%) were extranodal and 48 were non-AIDS related PCNSL accounting for 4.2% of extranodal NHL and 1.5% of all NHL, respectively. The average annual incidence rate of non-AIDS related PCNSL during the period was 1.56 cases per million population (age range: 15-85 yrs, median: 62 yrs, M/F ratio: 1). In a 23-year period there was no trend towards an increasing incidence of non-AIDS related PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary malignant brain tumors. Incidence of primary malignant brain tumors was stable, except for age ranges over 70 years. However, diagnostic artifacts might be responsible for this apparent increase. Histologically, 85% were high grade. Using the Kiel classification centroblastic diffuse (60%) and immunoblastic lymphoma (13%) were the most common subtypes. Forty-three patients had B-cell lymphoma and no T-cell lymphoma was detected. Forty-seven cases were diagnosed pre mortem. Treatment included surgical resection (26 patients), whole brain irradiation (WBRT) (43 patients) and chemotherapy (28 patients). Median survival for those receiving either WBRT or WBRT and chemotherapy was 8 months and 20 months, respectively (p = 0.78). Overall survival was 53%, 38% and 26% at 1, 2 and 5 years. Cox-regression analysis identified only one factor having independent impact on survival in PCNSL: performances score > or = 2 (p < 0.001, RR = 5.8).

By fluorescence microscopy (FM), flow cytometry (FCM) and immunoelectron microscopy (IEM) we have shown that B1 and B2 monoclonal antibodies (MoAbs) were able to induce modulation of CD20 and CD21 in RAJI and JOK-1 cell lines. Redistribution and internalization of both antigens (Ags) after binding with MoAbs was readily demonstrated by FM, and by IEM CD20 and CD21 were found to be processed by the pathway of receptor-mediated endocytosis. The rate of intracellular transport varied: CD21 > CD20 and RAJI > JOK-1. Approximately 65 and 55% of CD20 and 60 and 45% of CD21 were cleared from the surface of RAJI and JOK-1 cells, respectively (FCM and IEM). These values, however, clearly exceeded those corresponding to internalization (11, 9, 24 and 16%) indicating shedding of Ag-MoAb complexes. No evidence of recycling was found. The present data support the hypothesis that the kinetics of modulation vary from one Ag to another and probably also reflect the stage of differentiation of the malignant B-cells. The results are discussed in the context of the possible usefulness of B1 and B2 MoAbs in the therapy of B-cell malignancies.

European Journal of HaematologyVolume 53, Issue 4 p. 249-250 GM-CSF treatment of a patient with hairy-cell leukaemia. A potentially effective treatment? Niels Anker Peterslund, Niels Anker Peterslund Department of Medicine and Haematology, Knud Bendix, Department of Pathology, Aarhus University Hospital, Amtssygehuset, DK-8000 Aarhus C, DenmarkSearch for more papers by this authorAnne-Marie Boesen, Anne-Marie Boesen Department of Medicine and Haematology, Knud Bendix, Department of Pathology, Aarhus University Hospital, Amtssygehuset, DK-8000 Aarhus C, DenmarkSearch for more papers by this author Niels Anker Peterslund, Niels Anker Peterslund Department of Medicine and Haematology, Knud Bendix, Department of Pathology, Aarhus University Hospital, Amtssygehuset, DK-8000 Aarhus C, DenmarkSearch for more papers by this authorAnne-Marie Boesen, Anne-Marie Boesen Department of Medicine and Haematology, Knud Bendix, Department of Pathology, Aarhus University Hospital, Amtssygehuset, DK-8000 Aarhus C, DenmarkSearch for more papers by this author First published: October 1994 https://doi.org/10.1111/j.1600-0609.1994.tb00201.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume53, Issue4October 1994Pages 249-250 RelatedInformation

Antibody-induced antigenic modulation (AIAM) of CD10 and CD19 was studied on NALM-6, RAJI, and JOK-1 cell lines using fluorescence microscopy (FM), flow cytometry (FCM), and immunoelectron microscopy (IEM). Cross-linking with monoclonal antibodies (MoAbs) induced rapid redistribution of CD10 and CD19 on the cell surface (FM) followed by internalization involving uptake through plasmalemmal pits, transfer through endosomal compartment (receptor-mediated endocytosis), and, finally, delivery to lysosomes for degradation or exocytosis and recycling (IEM). Significant quantitative differences regarding modulation and intracellular processing were shown by FCM and IEM. Thus, 35%, 30%, and 25% of CD10 compared with 80%, 60%, and 40% of CD19 were internalized in NALM-6, RAJI, and JOK-1 cells, respectively. Also, the rate of intracellular transfer as well as externalization and recycling was more pronounced in the case of CD19 than of CD10 and in the NALM-6 and RAJI cells compared with the JOK-1 cells. These differences may possibly reflect the functional significance of CD10 and CD19 as well as the stage of differentiation of the malignant B cells. Although both antigens can be useful in MoAb-targeted immunotherapy, our findings suggest that anti-CD19 MoAbs would be preferable for delivery of cytotoxic agents to malignant B cells.

During the period January 1983 to January 1988 1597 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) were included in a Western Danish population-based NHL registry. Of these, 31% (N = 496) were low-grade NHL (LG-NHL) consisting of (Kiel): 9% lymphocytic (LY), 27% lymphoplasmacytic/-cytoid (IC), 53% follicular centroblastic/-centrocytic (CB/CCf) and 11% unclassifiable low-grade. LG-NHL (age range: 26-94 yrs, median: 64 yrs; M/F ratio: 0.8) had an age-standardised incidence rate (IR) of 2.7/10(5)/yr. Age-specific IR's showed an age-related exponential rise in all subtypes except for CB/CCf. Compared with the intermediate (IG)- and high-grade (HG) group, LG-NHL had more female cases (M/F ratio: 0.79 vs. 1.2; p = 0.0002), a higher frequency of stage III-IV disease (66% vs. 53%; p < 0.00005) and of bone marrow involvement (39% vs. 19%; p < 0.00005). A later revision of all IC cases (N = 132) distinguished 79 non-polymorphic (ICnp) from 25 polymorphic (ICp) cases; 28 cases were differently classified. In 34 LG-NHL patients histologic transformation was verified: CB/CCf to CB diffuse (22 pts) and LY to immunoblastic or CB type (6 pts). The 7-yr survival for LG-NHL was 63% (IG: 48%, HG: 38%; p < 0.00005). A Cox-regression analysis identified the following adverse prognostic factors for survival in LG-NHL: age > 50 with a relative risk (RR) of 3.2, hepatic involvement (RR = 2.1), elevated s-LDH (RR = 1.9), B-symptoms (RR = 1.8) and IC histology (ICnp+ICp) (RR = 1.7).(ABSTRACT TRUNCATED AT 250 WORDS)

A regimen of aclarubicin (ACR) of 75 mg/m2 daily for 3 days plus a continuous intravenous infusion of cytosine arabinoside (ara-C) of 100 mg/m2 per day for 7 days was compared with daunorubicin (DNR) 45 mg/m2/day for 3 days plus ara-C for 7 days as first-line chemotherapy of de novo acute myeloid leukemia (AML) in a randomized, nationwide Danish study. A total of 180 patients aged between 17 and 65 years were entered onto the protocol. Patients who achieved complete remission (CR) were given five courses of intensive consolidation therapy consisting of two courses of high dose ara-C, two courses of amsacrine plus etoposide, and one course of DNR plus ara-C. Of 174 evaluable patients, 99 achieved CR. The rate of CR was significantly higher on ACR plus ara-C than on DNR plus ara-C [66% versus 50% (p = 0.043)] and decreased significantly with increasing age. The hematological toxicity was identical for the two regimens. A total of 83 patients entered consolidation therapy. At 4 years, 37% of patients with CR following ACR were still in remission compared with 33% following DNR (p = 0.48), and the total survival at 4 years was 29% versus 20% (p = 0.26). The duration of remission and total survival both decreased with increasing age. ACR plus ara-C seem at least as good or better than DNR plus ara-C as first-line chemotherapy of AML.

A regimen of aclarubicin (ACR) of 75 mg/m2 daily for 3 days plus a continuous intravenous infusion of cytosine arabinoside (ara-C) of 100 mg/m2 per day for 7 days was compared with daunorubicin (DNR) 45 mg/m2/day for 3 days plus ara-C for 7 days as first-line chemotherapy of de novo acute myeloid leukemia (AML) in a randomized, nationwide Danish study. A total of 180 patients aged between 17 and 65 years were entered onto the protocol. Patients who achieved complete remission (CR) were given five courses of intensive consolidation therapy consisting of two courses of high dose ara-C, two courses of amsacrine plus etoposide, and one course of DNR plus ara-C. Of 174 evaluable patients, 99 achieved CR. The rate of CR was significantly higher on ACR plus ara-C than on DNR plus ara-C [66% versus 50% (p = 0.043)] and decreased significantly with increasing age. The hematological toxicity was identical for the two regimens. A total of 83 patients entered consolidation therapy. At 4 years, 37% of patients with CR following ACR were still in remission compared with 33% following DNR (p = 0.48), and the total survival at 4 years was 29% versus 20% (p = 0.26). The duration of remission and total survival both decreased with increasing age. ACR plus ara-C seem at least as good or better than DNR plus ara-C as first-line chemotherapy of AML.

With the object of evaluating three recognized prognostic stage subdivision systems for myelomatosis, retrospective data from 138 patients treated from 1976 to 1986 were employed. During this period, uniform therapeutic principles were employed, viz interval treatment with melphalan and prednisone supplemented, in cases of anaemia or raised serum creatinine, with vincristine. The prognostic significance for survival was calculated from variables at the time of diagnosis. The major prognostic factors were: age, tumour cell mass assessed by plasma cell percentage in the bone-marrow aspirate and/or M-component concentration, demonstration of Bence-Jones protein, renal function and the haemoglobin and calcium concentrations in the blood. Stage subdivision according the principles established by the Medical Research Council based on haemoglobin concentration and renal function were the best for assessing the prognosis in treated patients. Autopsy was performed on 55 out of the 96 patients who had died. The commonest cause of death was infection (75%).

Even though much is known about the presence of the common acute lymphoblastic leukemia antigen (CALLA) with respect to its distribution in hematopoietic and non-hematopoietic tissues, its functional role in lymphoid cells is as yet unknown. Given the fact that CALLA is completely modulated on the surface of lymphoid cells, we have employed pre-embedding immunogold techniques at electron-microscopical level and demonstrated that J5 monoclonal antibody (MoAb)-mediated modulation of CALLA expression on the lymphoblastic cell line NALM-6 is a specific, rapid process, closely resembling receptor-mediated endocytosis. Furthermore, it was found that CALLA was internalized through plasmalemmal pits and cytoplasmic vesicles and processed intracellularly in multivesicular bodies and secondary lysosomes. In contrast, HLA-DR antigen remained at the cell surface upon contact with specific MoAb. These data suggest that CALLA might be a receptor for a hitherto unknown signal molecule.