• Use of recombinant human deoxyribonuclease (DNase) for processing of a thawed umbilical cord blood transplant in a patient with relapsed acute

• Anti-Erwinia asparaginase antibodies during treatment of childhood acute lymphoblastic leukemia and their relationship to outcome: a case-control

• A successful second unrelated BMT (UBMT) from a different unrelated donor to treat ALL that relapsed after the initial UBMT.

• Mechanisms of the apoptotic activity of Cl-F-araA in a human T-ALL cell line, CCRF-CEM.

• [Echocardiographic assessment of circulation system in patients during and 3-5 years after all therapy in childhood]

• Acute lymphoblastic leukemia: optimizing treatment strategies in children.

• A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias.

• Efficacy of imatinib mesylate (STI571) in conjunction with alpha-interferon: long-term quantitative molecular remission in relapsed

• A single, high dose of idarubicin combined with cytarabine as induction therapy for adult patients with recurrent or refractory acute

• Beginning treatment for childhood acute lymphoblastic leukemia: insights from the parents' perspective.

• Mild axonal neuropathy of children during treatment for acute lymphoblastic leukaemia.

• A parent's perspective: providing compassionate and effective care.

• [Adult T-cell leukemia/lymphoma. Therapeutic aspects]

1
UI - 11904746
AU - Eichler H; Beck C; Bernard F; Bugert P; Kluter H
TI - Use of recombinant human deoxyribonuclease (DNase) for processing of a thawed umbilical cord blood transplant in a patient with relapsed acute lymphoblastic leukemia.
SO - Ann Hematol 2002 Mar;81(3):170-3
AD - Institute of Transfusion Medicine and Immunology, Red Cross Blood Service of Baden-Wurttemberg-Hessen, College of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany. h.eichler@blutspende.de
This case report describes for the first time the use of a recombinant human enzyme deoxyribonuclease (rhDNase) containing solution for the processing of a thawed umbilical cord blood (UCB) unit prior to successful transplantation to avoid cell losses by clotting phenomena. A 6-year-old boy received an unrelated 2/6 HLA antigen mismatched UCB transplant for high-risk Burkitt type acute lymphoblastic leukemia. The UCB unit was provided as a volume-reduced sample after buffy coat separation with a final volume of 36 ml. To avoid the loss of nucleated cells due to cell clumping during thawing procedure cells were washed with a solution containing the rhDNase. No visible clotting of the resuspended unit occurred, and the patient was transplanted with 2.9x10(7) nucleated cells/kg body weight without any acute or chronic side effects due to rhDNase. On day +35, PCR analysis of bone marrow aspirate showed complete chimerism, and the child engrafted with an absolute neutrophil count greater than 0.5x10(9)/l on day +47. Platelet transfusion independence was achieved on day +120. In conclusion, the supplementation of rhDNase to the washing and resuspension solutions of a thawed UCB unit is effective to prevent cell losses prior to transplantation. However, further investigations must be performed to confirm the safety of this procedure.

2
UI - 12172975
AU - Klug Albertsen B; Schmiegelow K; Schroder H; Carlsen NT; Rosthoj S;
TI - Avramis VI; Jakobsen P Anti-Erwinia asparaginase antibodies during treatment of childhood acute lymphoblastic leukemia and their relationship to outcome: a case-control study.
SO - Cancer Chemother Pharmacol 2002 Aug;50(2):117-20
AD - Department of Pharmacology, The Bartholin Building, University of Aarhus, 8000 Aarhus C, Denmark. bka@farm.au.dk
PURPOSE: A case-control study was performed to determine whether patients who had been treated with Erwinia asparaginase as part of their treatment for childhood acute lymphoblastic leukemia (ALL) and who showed relapsed of their disease more often developed anti-asparaginase antibodies than patients who remained in remission. METHODS: A group of 13 patients who showed relapsed of their disease (median follow-up 35 months) were randomly matched with control patients of the same risk group (two control patients to each case), who had received therapy of the same intensity during the same period (median follow-up 70 months). Anti- Erwinia asparaginase antibodies were measured (ELISA method) during maintenance therapy after asparaginase treatment (30,000 IU/m(2) daily for 10 days in all patients plus twice weekly for 2 weeks in intermediate-risk and high-risk ALL patients). RESULTS: The overall incidence of anti- Erwinia asparaginase antibodies was 8% (3 of 39 patients). There was no statistically significant difference in the incidence of antibody formation between patients who had suffered relapse (1 of 13) and those who had not (2 of 26). In two of the three patients who developed antibodies, the antibodies disappeared after some time, whereas one patient had measurable antibody levels for more than a year after asparaginase therapy. CONCLUSIONS: In this study, the development of anti-Erwinia asparaginase antibodies was rare and was unrelated to the risk of relapse.

3
UI - 12221672
AU - Uehara T; Nakaseko C; Yokota A; Saito Y; Nishimura M
TI - A successful second unrelated BMT (UBMT) from a different unrelated donor to treat ALL that relapsed after the initial UBMT.
SO - Am J Hematol 2002 Sep;71(1):37-40
AD - Second Department of Internal Medicine, Chiba University Graduate School of Medicine, Chiba City, Chiba, Japan.
A 26-year-old male with acute lymphoblastic leukemia (ALL) in its second complete remission received an unrelated bone marrow transplantation (UBMT) following cyclophosphamide plus total body irradiation conditioning. The patient relapsed 7 months after the BMT. He received a second UBMT from a different donor 15 months after the initial UBMT. Conditioning for the second UBMT consisted of busulphan, melphalan, and anti-thymocyte globulin. The regimen was well tolerated, and engraftment was achieved. Both acute and chronic graft-versus-host diseases occurred but were successfully controlled with immunosuppressive drugs. He is alive and disease-free 29 months after the second UBMT. This is the first report of a successful second UBMT for ALL that had relapsed after the first UBMT and for which a different donor was used. Copyright 2002 Wiley-Liss, Inc.

4
UI - 12203101
AU - Takahashi T; Shimizu M; Akinaga S
TI - Mechanisms of the apoptotic activity of Cl-F-araA in a human T-ALL cell line, CCRF-CEM.
SO - Cancer Chemother Pharmacol 2002 Sep;50(3):193-201
AD - Department of Oncology, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co. Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8731, Japan.
PURPOSE: The purpose of the present study was to characterize the mechanisms of the antitumor activity of 2-chloro-9-(2-deoxy-2-fluoro-beta- D-arabinofuranosyl)adenine (Cl-F-araA) against lymphocytic leukemia. Recent evidence indicates that Cl-F-araA has more potent antitumor activity in vitro against human leukemia cell lines than against human solid tumor cell lines originating from different tissue. We analyzed the mechanism of action of Cl-F-araA using a human T-acute lymphocytic leukemia cell line, CCRF-CEM, in vitro and in vivo. RESULTS: Cl-F-araA exhibited marked antitumor activity in vitro and in vivo, and this was correlated with its ability to induce apoptosis, particularly in vivo. To analyze the mechanisms of the apoptotic activity of Cl-F-araA, we sought to determine the effects of the drug on the levels of Bcl-2 family proteins (Bcl-2, Bcl-X(L), Mcl-1, Bax, Bak) and cell survival signals via Akt. Western blot analysis revealed that Cl-F-araA induced a dose- and time-dependent downregulation of Bcl-X(L) and Mcl-1 proteins, and a dose- and time-dependent dephosphorylation of Akt and its downstream effectors (Bad, FKHRL1), particularly in vivo. In addition, there was a marked increase in the population of cells in G(1)/S and early S phase. We therefore investigated the changes in the Cdc25A protein to characterize the mechanism involved in the G(1)/S accumulation. Cl-F-araA induced a dose- and time-dependent downregulation of the Cdc25A protein whereas the Cdc25C protein remained unchanged. We further found that in combination with caffeine, Cl-F-araA potentiated apoptosis induction. CONCLUSIONS: Taken together, our findings suggest that Cl-F-araA may be an effective drug in vivo.

5
UI - 12182001
AU - Ostanski M; Sonta-Jakimczyk D
TI - [Echocardiographic assessment of circulation system in patients during and 3-5 years after all therapy in childhood]
SO - Wiad Lek 2002;55(3-4):164-73
AD - Katedry i Kliniki Hematologii Dzieciecej i Chemioterapii w Zabrzu.
Circulatory disturbances may occur during and after the treatment of acute lymphoblastic leukemia (ALL). The reasons are: leukemic infiltrations of the heart, anaemia, renal disturbances, infections, cardiotoxic drugs, especially anthracyclines (Atc). The aim of the study was echocardiographic assessment of circulatory system in patients during and 3-5 years after ALL therapy in childhood. The study group (group B) consisted of 20 children, aged 1-16 years, who underwent Atc treatment with cumulative doses 155.8-330 mg/m2 and cardioprotective agent--dexrazoxane. In this group echocardiography was performed before the treatment as well as after 1, 6, 12 months and 3 years. The retrospective group (R) consisted of 36 persons aged 12-24 years, examined 3-5 years after the completion of ALL treatment, who had undergone the treatment with Atc in doses 148.6-416.7 mg/m2 without cardioprotection. The control group (K) consisted of 28 healthy volunteers, aged 9-25 years. In all subjects echocardiography was performed, standard measurements taken, systolic and diastolic indices of left ventricle (LV) function calculated. In patients during and 3-5 years after the treatment neither LV dilatation nor abnormal wall-thickness was found. The systolic indices remained normal. In the group B echocardiographic indices did not change significantly during 3 years of treatment and did not correlate with growing cumulative Atc doses. In this group isovolumetric relaxation time (IVRT) was significantly longer, what emphasized the need of further clinical and echocardiographic follow-up.

6
UI - 12038876
AU - Vora A
TI - Acute lymphoblastic leukemia: optimizing treatment strategies in children.
SO - Paediatr Drugs 2002;4(6):405-16
AD - Department of Paediatric Haematology, Sheffield Children's Hospital, Sheffield, England. ajay.vora@sch.nhs.uk
After the substantial improvements in cure rates for childhood acute lymphoblastic leukemia (ALL) obtained with intensified treatment strategies in the 1970s and 1980s, the last decade has seen slower progress on several fronts. Long-term follow-up has revealed late treatment-related adverse effects and focused attention on risk-targeted therapy to minimize adverse effects in patients at standard risk. Advances in the understanding of the biological features of childhood ALL have provided a platform for the development of such risk-directed protocols. At the same time, salvage of patients who have relapsed has improved such that 5-year overall survival rates are approaching 85%. The United Kingdom Medical Research Council Childhood Leukaemia Working Party has conducted trials of childhood ALL therapy (UKALL protocols) since the late 1960s. Early studies (UKALL I, II, III and V) focused on randomized testing of various aspects of the St Judes' first total therapy protocol. Later studies have confirmed the benefit of intensified therapy (UKALL X and XI), and shown that standard risk patients do not need cranial radiotherapy to prevent central nervous system relapse. UKALL R1 and R2 documented the efficacy of salvage chemotherapy. Improvements in infant ALL outcome have been less impressive and 5-year event free survival is still a disappointing 40%. Future strategies will incorporate more specific risk-directed therapy and greater international collaboration.

7
UI - 12200353
AU - Ottmann OG; Druker BJ; Sawyers CL; Goldman JM; Reiffers J; Silver RT;
TI - Tura S; Fischer T; Deininger MW; Schiffer CA; Baccarani M; Gratwohl A; Hochhaus A; Hoelzer D; Fernandes-Reese S; Gathmann I; Capdeville R; O'Brien SG A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias.
SO - Blood 2002 Sep 15;100(6):1965-71
AD - Medizinische Klinik III/Abteilung Haematologie, Johann Wolfgang Goethe Universitat, 60590 Frankfurt, Germany. ottmann@em.uni-frankfurt.de
The translocation (9;22) gives rise to the p190(Bcr-Abl) and p210(Bcr-Abl) tyrosine kinase proteins, considered sufficient for leukemic transformation. Philadelphia-positive (Ph(+)) acute leukemia patients failing to respond to initial induction therapy have a poor prognosis with few effective treatment options. Imatinib is an orally administered, potent inhibitor of the Bcr-Abl tyrosine kinase. We conducted a clinical trial in 56 patients with relapsed or refractory Ph(+) acute lymphoblastic leukemia (ALL; 48 patients) or chronic myelogenous leukemia in lymphoid blast crisis (LyBC; 8 patients). Imatinib was given once daily at 400 mg or 600 mg. Imatinib induced complete hematologic responses (CHRs) and complete marrow responses (marrow-CRs) in 29% of ALL patients (CHR, 19%; marrow-CR, 10%), which were sustained for at least 4 weeks in 6% of patients. Median estimated time to progression and overall survival for ALL patients were 2.2 and 4.9 months, respectively. CHRs were reported for 3 (38%) of the patients with LyBC (one sustained CHR). Grade 3 or 4 treatment-related nonhematologic toxicity was reported for 9% of patients; none of the patients discontinued therapy because of nonhematologic adverse reactions. Grade 4 neutropenia and thrombocytopenia occurred in 54% and 27% of patients, respectively. Imatinib therapy resulted in a clinically relevant hematologic response rate in relapsed or refractory Ph(+) acute lymphoid leukemia patients, but development of resistance and subsequent disease progression were rapid. Further studies are warranted to test the effects of imatinib in combination with other agents and to define the mechanisms of resistance to imatinib.

8
UI - 12357372
AU - Visani G; Isidori A; Malagola M; Alberti D; Capdeville R; Martinelli G;
TI - Piccaluga PP; Amabile M; Guiducci B; Tura S; Baccarani M Efficacy of imatinib mesylate (STI571) in conjunction with alpha-interferon: long-term quantitative molecular remission in relapsed P-190(BCR-ABL)-positive acute lymphoblastic leukemia.
SO - Leukemia 2002 Oct;16(10):2159-60

9
UI - 12209751
AU - Weiss MA; Aliff TB; Tallman MS; Frankel SR; Kalaycio ME; Maslak PG;
TI - Jurcic JG; Scheinberg DA; Roma TE A single, high dose of idarubicin combined with cytarabine as induction therapy for adult patients with recurrent or refractory acute lymphoblastic leukemia.
SO - Cancer 2002 Aug 1;95(3):581-7
AD - Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
BACKGROUND: The majority of adult patients who are treated for lymphoblastic disease will either develop recurrent disease or will be refractory to their initial therapy. One option for patients with recurrent/refractory disease is to administer a reinduction regimen that employs a dose-intense combination of anthracycline and cytarabine. These salvage regimens are relatively distinct from the traditional vincristine/prednisone-based programs that are used typically as primary induction therapy. The authors studied a regimen that contained high-dose cytarabine and a single high dose of idarubicin as salvage induction therapy for patients with recurrent or refractory lymphoblastic disease. METHODS: Twenty-nine previously treated adult patients with recurrent or refractory acute lymphoblastic leukemia were treated with a new intensive regimen. Eight patients had primary refractory disease. Twenty-one patients had recurrent disease, and 16 of these patients developed recurrent disease while they were still receiving their primary therapy. The treatment regimen consisted of cytarabine 3.0 g/m(2) by 3-hour infusion daily for 5 days and idarubicin 40 mg/m(2) given as a single dose on Day 3. Filgrastim (granulocyte-colony stimulating factor) 5 microg/kg administered subcutaneously every 12 hours was started on Day 7 and was continued until the absolute neutrophil count was > 5000/microL. Response was assessed using standard criteria. RESULTS: There were 11 complete responses (38%; 95% confidence interval, 20-56%). Four patients subsequently underwent allogeneic bone marrow transplantation. Moderate but acceptable toxicity was observed given the severely myelosuppressive nature of the regimen. There was only one treatment-related death (3%). Two patients, both with significant prior exposure to anthracyclines, suffered reductions in left ventricular function to the 20-30% range during episodes of severe systemic infection. After recovery from infection, the ejection fraction in one patient improved to 50%. CONCLUSIONS: The authors conclude that this regimen has moderate activity and a relatively low incidence of mortality for this high-risk group of patients. This regimen may be most suitable for patients who can undergo potentially curative allogeneic bone marrow transplantation if they achieve a complete response. Copyright 2002 American Cancer Society.

10
UI - 12096296
AU - McGrath P
TI - Beginning treatment for childhood acute lymphoblastic leukemia: insights from the parents' perspective.
SO - Oncol Nurs Forum 2002 Jul;29(6):988-96
AD - University of Queensland, St. Lucia, Australia. p.mcgrath@uq.edu.au
PURPOSE/OBJECTIVES: To report the perspective of parents during the initial stages of diagnosis and treatment for their children's acute lymphoblastic leukemia (ALL). DESIGN: Descriptive and phenomenologic. SETTING: Royal Children's Hospital, Brisbane, Australia. SAMPLE: Parents (mothers, n = 12; fathers, n = 4) of 12 children (ages 0-10) undergoing treatment for ALL. METHODS: Open-ended, audiotaped interviews were transcribed verbatim and analyzed. MAIN RESEARCH VARIABLES: Parents' experiences of their children's initial diagnosis and treatment of ALL. FINDINGS: The parents' insights provided a clear indication that the initial stage of treatment is highly stressful and parents may be overwhelmed by the experience. The situational stress translated into three potentially overwhelming emotional states: the stress of uncertainty, the shock of diagnosis, and a feeling of being trapped in an unpleasant emotional roller-coaster ride. Honesty from healthcare professionals, the opportunity to share feelings, and an affirmation of the harshness of the situation were reported as helpful in dealing with the sense of being overwhelmed. CONCLUSION: Parents need honest information and sensitive emotional support to come to terms with the stresses associated with their children's diagnosis and initial treatment of ALL. Parents must have access to a safe environment where they can express their feelings and have the harsh reality of the initial stage of treatment affirmed. IMPLICATIONS FOR NURSING: Parents need considerable emotional support to negotiate the initial stage of treatment for ALL. Parents of children diagnosed with ALL must have honest information about diagnosis and treatment, as much information as possible for planning their daily lives, an opportunity to express real feelings, access to moments of personal space where feelings can be processed, and compassionate understanding of the emotional difficulties associated with this difficult life journey.

11
UI - 11030069
AU - Reinders-Messelink HA; Van Weerden TW; Fock JM; Gidding CE; Vingerhoets
TI - HM; Schoemaker MM; Goeken LN; Bokkerink JP; Kamps WA Mild axonal neuropathy of children during treatment for acute lymphoblastic leukaemia.
SO - Eur J Paediatr Neurol 2000;4(5):225-33
AD - Children's Cancer Center Groningen, University of Groningen, The Netherlands.
Neurophysiological functioning was studied prospectively in children treated for acute lymphoblastic leukaemia with a low dose vincristine regime (8 x 1.5 mg/m2/dose), to obtain more insight into vincristine neuropathy. A WHO neurotoxicity score was estimated and vibration sense and electrophysiological measurements were taken at standardized times during vincristine treatment. The WHO neurotoxicity score showed decreased or disappearance of Achilles tendon reflexes, and mild sensory disturbances, but a grade 3-4 neurotoxicity was not demonstrated by any of the children. Vibration perception thresholds increased progressively during treatment and amplitudes of action potentials of peroneal and sensory ulnar and median nerves decreased, whereas nerve conduction velocities stayed unchanged. Both vibration perception thresholds and the electrophysiological findings hardly exceeded the limits of normality. We conclude that children treated for acute lymphoblastic leukaemia with a low dose vincristine regimen have mild axonal neuropathy which may be responsible for the motor problems in these children.

12
UI - 11494601
AU - McDonald V
TI - A parent's perspective: providing compassionate and effective care.
SO - Hosp Q 1999-2000 Winter;3(2):20-4

13
UI - 12385063
AU - Besson C; Plumelle Y; Arnulf B; Gonin C; Panelatti G; Bazarbachi A;
TI - Hermine O [Adult T-cell leukemia/lymphoma. Therapeutic aspects]
SO - Presse Med 2001 Feb 10;30(5):243-5
AD - Service d'Hematologie clinique, Hopital Necker, 149, rue de Sevres, F75743 Paris.
CONVENTIONAL CHEMOTHERAPY: Complete remission of aggressive ATL (acute or lymphomatous forms) can be achieved in about 40% of the patients with conventional chemotherapy, but early relapse and infectious complications is the rule. For painless and chronic ATL, chemotherapy does not appear to be useful and can aggravate the immunodepression. NEW THERAPEUTIC APPROACHES: Encouraging results have been obtained with a combination regimen using an antiretroviral agent (AZT) and interferon alpha. Response rate has been high with good tolerance. In responders, the survival rate is better than with conventional chemotherapy. PERSPECTIVES: The success of a potentially antiretroviral approach for the treatment of this generally chemoresistant disease suggests that HTLV-1 virus could have a continuous effect on in vivo leukomogenesis.

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