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Fulltext Disseminated fusariosis and endogenous fungal endophthalmitis in acute lymphoblastic leukemia following platelet transfusion possibly due to transfusion-related immunomodulation

Kah TA, Yong KC, Rahman RA

BMC Ophthalmol, 2011;11:30.
PMID: 22044440 DOI: 10.1186/1471-2415-11-30

To report a case of disseminated fusariosis with endogenous endophthalmitis in a patient with acute lymphoblastic leukemia. Transfusion-associated immune modulation secondary to platelet transfusion could play an important role in the pathophysiology of this case.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*
Haematological remission induced by donor leukocytes infusion in a case of Philadelphia positive acute lymphoblastic leukaemia relapsing after allogeneic bone marrow transplantation

Saw MH, Teh A, Wong HC, Bosco J

Int J Hematol, 1997 Feb;65(2):173-8.
PMID: 9071823
Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*
Fulltext Second malignant neoplasms: an increasingly recognized complication of childhood cancer

Ariffin H, Ariffin WA, Chan LL, Lam SK, Lin HP

Med J Malaysia, 1997 Jun;52(2):174-7.
PMID: 10968078

Second malignant neoplasms (SMN) are an increasingly recognized late complication seen in childhood cancer survivors. A total of 3 cases of SMN have been found in the Department of Paediatrics, University Hospital Kuala Lumpur after a 15-year experience of treating childhood malignancies. Two cases are described here. The first developed abdominal non-Hodgkin's lymphoma 3 years after undergoing an allogeneic bone marrow transplant for second relapse of acute lymphoblastic leukaemia, while the second child developed myeloid leukaemia two years after completing treatment for acute lymphoblastic leukaemia. Progress in the management of childhood cancer in Malaysia and the availability of bone marrow transplantation facilities have increased the number of childhood cancer survivors; leading to increased incidence of SMN.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
Fulltext Comparison of reduced-intensity and myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia and acute lymphoblastic leukemia: a meta-analysis

Abdul Wahid SF, Ismail NA, Mohd-Idris MR, Jamaluddin FW, Tumian N, Sze-Wei EY, et al.

Stem Cells Dev, 2014 Nov 1;23(21):2535-52.
PMID: 25072307 DOI: 10.1089/scd.2014.0123

Currently, the indications to perform reduced-intensity conditioning allogeneic hematopoietic stem cell transplant (RIC-HCT) are based on data derived mainly from large registry and single-centre retrospective studies. Thus, at the present time, there is limited direct evidence supporting the current practice in selecting patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) for RIC versus myeloablative conditioning (MAC) transplants. To determine the relationship between dose intensity of conditioning regimen and survival outcomes after allografting in AML/ALL patients, we performed a meta-analysis of 23 clinical trials reported between 1990 and 2013 involving 15,258 adult patients that compare survival outcomes after RIC-HCT versus MAC-HCT. RIC-HCT resulted in comparable <2-year and 2-6 year overall survival (OS) rates post-transplantation even though the RIC-HCT recipients were older and had more active disease than MAC-HCT recipients. The 2-6 year progression-free survival (PFS), nonrelapse mortality, acute graft-versus-host disease (GvHD) and chronic GvHD rates were reduced after RIC-HCT, but relapse rate was increased. Similar outcomes were observed regardless of disease type and status at transplantation. Odds ratio for all outcomes remained comparable with or without performing separate analyses for the year of HCT and for retrospective versus prospective studies. Among RIC-HCT recipients, survival rates were superior if patients were in CR at transplantation. Significant inter-study heterogeneity for aGvHD data and publication bias for PFS data were observed. This meta-analysis showed no OS benefit of MAC-HCT over RIC-HCT across the entire cohort of patients suggesting that RIC-HCT could be an effective therapeutic option for AML/ALL patients who are ineligible for MAC-HCT and CR status is preferred before RIC-HCT.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*
Fulltext Minimal residual disease-guided treatment deintensification for children with acute lymphoblastic leukemia: results from the Malaysia-Singapore acute lymphoblastic leukemia 2003 study

Yeoh AE, Ariffin H, Chai EL, Kwok CS, Chan YH, Ponnudurai K, et al.

J Clin Oncol, 2012 Jul 1;30(19):2384-92.
PMID: 22614971 DOI: 10.1200/JCO.2011.40.5936

PURPOSE: To improve treatment outcome for childhood acute lymphoblastic leukemia (ALL), we designed the Malaysia-Singapore ALL 2003 study with treatment stratification based on presenting clinical and genetic features and minimal residual disease (MRD) levels measured by polymerase chain reaction targeting a single antigen-receptor gene rearrangement.
PATIENTS AND METHODS: Five hundred fifty-six patients received risk-adapted therapy with a modified Berlin-Frankfurt-Münster-ALL treatment. High-risk ALL was defined by MRD ≥ 1 × 10(-3) at week 12 and/or poor prednisolone response, BCR-ABL1, MLL gene rearrangements, hypodiploid less than 45 chromosomes, or induction failure; standard-risk ALL was defined by MRD ≤ 1 × 10(-4) at weeks 5 and 12 and no extramedullary involvement or high-risk features. Intermediate-risk ALL included all remaining patients.
RESULTS: Patients who lacked high-risk presenting features (85.7%) received remission induction therapy with dexamethasone, vincristine, and asparaginase, without anthracyclines. Six-year event-free survival (EFS) was 80.6% ± 3.5%; overall survival was 88.4% ± 3.1%. Standard-risk patients (n = 172; 31%) received significantly deintensified subsequent therapy without compromising EFS (93.2% ± 4.1%). High-risk patients (n = 101; 18%) had the worst EFS (51.8% ± 10%); EFS was 83.6% ± 4.9% in intermediate-risk patients (n = 283; 51%).
CONCLUSION: Our results demonstrate significant progress over previous trials in the region. Three-drug remission-induction therapy combined with MRD-based risk stratification to identify poor responders is an effective strategy for childhood ALL.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*
CD26: A Prognostic Marker of Acute Lymphoblastic Leukemia in Children in the Post Remission Induction Phase

Mehde AA, Yusof F, Adel Mehdi W, Zainulabdeen JA

Asian Pac J Cancer Prev, 2015;16(12):5059-62.
PMID: 26163641

BACKGROUND: ALL is an irredeemable disease due to the resistance to treatment. There are several influences which are involved in such resistance to chemotherapy, including oxidative stress as a result of the generation of reactive oxygen species (ROS) and presence of hypodiploid cells. Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase-4, is a 110 kDa, multifunctional, membrane-bound glycoprotein.
AIM AND OBJECTIVES: The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status.
MATERIALS AND METHODS: CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione- s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase.
RESULTS: The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients.
CONCLUSIONS: Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
Fulltext Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study

Peters C, Dalle JH, Locatelli F, Poetschger U, Sedlacek P, Buechner J, et al.

J Clin Oncol, 2021 02 01;39(4):295-307.
PMID: 33332189 DOI: 10.1200/JCO.20.02529

PURPOSE: Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients.
PATIENTS AND METHODS: FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129).
RESULTS: Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; P < .0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; P < .0001) and 0.02 (95% CI, < 0.01 to 0.05; P = .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively.
CONCLUSION: Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*
Fulltext Breast and ovarian recurrence of acute lymphoblastic leukaemia after allogeneic peripheral blood haematopoietic stem cell transplantation

Fadilah SA, Goh KY

Singapore Med J, 2009 Dec;50(12):e407-9.
PMID: 20087541

Breast recurrence of acute lymphoblastic leukaemia (ALL) after stem cell transplant is uncommon, with less than 20 reported cases in the literature. In the majority of cases, the lesions developed without simultaneous involvement of other sites or graft-versus-host disease (GvHD). We describe the first case of simultaneous bilateral breast and ovarian relapses after allografting in ALL, occurring in an 18-year-old female Chinese patient while she was having oral and hepatic chronic GvHD, persistent haematological remission and donor haematopoiesis. She received radiotherapy and chemotherapy, which resulted in resolution of the breast and ovarian lesions, and remained disease free ten months after the onset of the relapse. This case suggests that there may be different mechanisms for bone marrow vs. extramedullary relapses and a complex relationship between GvHD and graft-versus-leukaemia.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*