scholarly journals Other (Non-CNS/Testicular) Extramedullary Localizations of Childhood Relapsed Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma—A Report from the ALL-REZ Study Group

2021 ◽  
Vol 10 (22) ◽  
pp. 5292
Author(s):  
Andrej Lissat ◽  
Claudia van Schewick ◽  
Ingo G. Steffen ◽  
Ayumu Arakawa ◽  
Jean-Pierre Bourquin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Cox Regression ◽  
Lymphoblastic Leukemia ◽  
Local Treatment ◽  
Local Therapy ◽  
Lymphoblastic Lymphoma ◽  
Prognostic Features ◽  
Extramedullary Relapse ◽  
Time To Relapse

Children with other extramedullary relapse of acute lymphoblastic leukemia are currently poorly characterized. We aim to assess the prevalence and the clinical, therapeutic and prognostic features of extramedullary localizations other than central nervous system or testis in children with relapse of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) treated on a relapsed ALL protocol. Patients and Methods: Patients with relapse of ALL and LBL, treated according to the multicentric ALL-REZ BFM trials between 1983 and 2015, were analyzed for other extramedullary relapse (OEMR) of the disease regarding clinical features, treatment and outcome. Local treatment/irradiation has been recommended on an individual basis and performed only in a minority of patients. Results: A total of 132 out of 2323 (5.6%) patients with ALL relapse presented with an OEMR (combined bone marrow relapse n = 78; isolated extramedullary relapse n = 54). Compared to the non-OEMR group, patients with OEMR had a higher rate of T-immunophenotype (p < 0.001), a higher rate of LBL (p < 0.001) and a significantly different distribution of time to relapse, i.e., more very early and late relapses compared to the non-OEMR group (p = 0.01). Ten-year probabilities of event-free survival (pEFS) and overall survival (pOS) in non-OEMR vs. OEMR were 0.38 ± 0.01 and 0.32 ± 0.04 (p = 0.0204) vs. 0.45 ± 0.01 and 0.37 ± 0.04 (p = 0.0112), respectively. OEMRs have been classified into five subgroups according to the main affected compartment: lymphatic organs (n = 32, 10y-pEFS 0.50 ± 0.09), mediastinum (n = 35, 10y-pEFS 0.11 ± 0.05), bone (n = 12, 0.17 ± 0.11), skin and glands (n = 21, 0.32 ± 0.11) and other localizations (n = 32, 0.41 ± 0.09). Patients with OEMR and T-lineage ALL/LBL showed a significantly worse 10y-pEFS (0.15 ± 0.04) than those with B-Precursor-ALL (0.49 ± 0.06, p < 0.001). Stratified into standard risk (SR) and high risk (HR) groups, pEFS and pOS of OEMR subgroups were in the expected range whereas the mediastinal subgroup had a significantly worse outcome. Subsequent relapses involved more frequently the bone marrow (58.4%) than isolated extramedullary compartments (41.7%). In multivariate Cox regression, OEMR confers an independent prognostic factor for inferior pEFS and pOS. Conclusion: OEMR is adversely related to prognosis. However, the established risk classification can be applied for all subgroups except mediastinal relapses requiring treatment intensification. Generally, isolated OEMR of T-cell-origin needs an intensified treatment including allogeneic stem cell transplantation (HSCT) as a curative approach independent from time to relapse. Local therapy such as surgery and irradiation may be of benefit in selected cases. The indication needs to be clarified in further investigations.

scholarly journals Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group

Blood ◽  
2008 ◽  
Vol 111 (6) ◽  
pp. 2984-2990 ◽  
Author(s):  
Stella M. Davies ◽  
Michael J. Borowitz ◽  
Gary L. Rosner ◽  
Kristin Ritz ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Response To Therapy ◽  
Oncology Group ◽  
Risk Status ◽  
Prognostic Features ◽  
Minimal Residual

Abstract Minimal residual disease (MRD) as a marker of antileukemic drug efficacy is being used to assess risk status and, in some cases, to adjust the intensity of therapy. Within known prognostic categories, the determinants of MRD are not known. We measured MRD by flow cytometry at day 8 (in blood) and at day 28 (in bone marrow) of induction therapy in more than 1000 children enrolled in Pediatric Oncology Group therapy protocols 9904, 9905, and 9906. We classified patients as “best risk” if they had cleared MRD by day 8 of therapy and as “worst risk” if they had MRD remaining in bone marrow at day 28, and tested whether MRD was related to polymorphisms in 16 loci in genes hypothesized to influence response to therapy in acute lymphoblastic leukemia (ALL). After adjusting for known prognostic features such as presence of the TEL-AML1 rearrangement, National Cancer Institute (NCI) risk status, ploidy, and race, the G allele of a common polymorphism in chemokine receptor 5 (CCR5) was associated with more favorable MRD status than the A allele (P = .009, logistic regression), when comparing “best” and “worst” risk groups. These data are consistent with growing evidence that both acquired and host genetics influence response to cancer therapy.

scholarly journals Acute Lymphoblastic Leukemia following Lenalidomide Maintenance for Multiple Myeloma: Two Cases with Unexpected Presentation and Good Prognostic Features

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Abdullah M. Khan ◽  
Jameel Muzaffar ◽  
Hermant Murthy ◽  
John R. Wingard ◽  
Jan S. Moreb
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Biopsy ◽  
Lymphoblastic Leukemia ◽  
Second Primary ◽  
Cell Transplant ◽  
Second Primary Malignancy ◽  
Primary Malignancy ◽  
Prognostic Features

Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance. ALL was unexpectedly diagnosed on bone marrow biopsy. One patient was diagnosed on routine biopsy performed as part of requirements of the clinical trial. Both patients had B-cell ALL, without known poor risk cytogenetics, and were managed with standard induction therapies resulting in complete remission. We also reviewed the literature for similar cases of secondary ALL (sALL) in MM patients exposed to immunomodulatory drugs (IMiDs). In conclusion, persistent cytopenias in responding MM patients receiving IMiDs maintenance should be an indication for bone marrow biopsy. Patients develop sALL after median of 32.5 months (range, 20–84) from being on lenalidomide or thalidomide maintenance, often presenting with cytopenias, display low tolerance to chemotherapy, but remission can often be achieved.

Toxicity and efficacy of intensive chemotherapy for children with acute lymphoblastic leukemia (ALL) after first bone marrow or extramedullary relapse

2004 ◽  
Vol 43 (5) ◽  
pp. 571-579 ◽  
Author(s):  
Blythe Thomson ◽  
Julie R. Park ◽  
Judy Felgenhauer ◽  
Soheil Meshinchi ◽  
John Holcenberg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Intensive Chemotherapy ◽  
Extramedullary Relapse

Significance of Mediastinal Mass in Acute Lymphoblastic Leukemia

PEDIATRICS ◽  
1975 ◽  
Vol 55 (6) ◽  
pp. 889-893
Author(s):  
Yaddanapudi Ravindranath ◽  
Joseph Kaplan ◽  
W. W. Zuelzer
Keyword(s):  
Bone Marrow ◽  
Retrospective Study ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Clinical Characteristics ◽  
Mediastinal Mass ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Involvement ◽  
Cell Tumor ◽  
Lymphoblastic Lymphoma

A mediastinal mass (MM) is found at the time of diagnosis in 10% to 15% of children with acute lymphoblastic leukemia (ALL).1 In view of the frequent progression of childhood mediastinal lymphoblastic lymphoma (MLL) to leukemia,2,3 ALL + MM may be MLL with early bone marrow involvement. We have found that MLL is a T cell tumor, while ALL is a tumor of cells with neither T nor B cell characteristics.4 Therefore, if ALL + MM is a leukemic stage of MLL, patients with ALL + MM and ALL may differ in their clinical characteristics and responses to therapy. To test this hypothesis, we conducted a retrospective study to compare children with ALL + MM and ALL followed in this clinic over the last seven years.

scholarly journals Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1166-1172 ◽  
Author(s):  
G Henze ◽  
R Fengler ◽  
R Hartmann ◽  
B Kornhuber ◽  
G Janka-Schaub ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Therapy Group ◽  
Lymphoblastic Leukemia ◽  
Cell Phenotype ◽  
Front Line ◽  
Extramedullary Relapse ◽  
Group A ◽  
First Relapse ◽  
Group B

Abstract Between April 1985 and March 1987 130 children and adolescents up to 18 years of age with first relapse of acute lymphoblastic leukemia (ALL) were registered on the stratified and randomized multicentric trial ALL- REZ BFM 85 designed for patients pretreated with intensive front-line therapies. Stratification criteria were time and site of relapse: bone marrow (BM) relapse on or up to 6 months after stopping front-line therapy (group A), BM relapse beyond 6 months after therapy (group B), and isolated extramedullary relapse at any time (group C). Treatment consisted of alternating courses of polychemotherapy including randomly administered high- or intermediate-dose methotrexate (HDMTX:12 g/m2 as 4-hour infusion; IDMTX: 1 g/m2 as 36-hour infusion). During maintenance therapy the patients received daily oral thioguanine and biweekly intravenous (IV) MTX. The overall second complete remission (CR) rate was 92% (groups A, B, and C: 88%, 92%, and 100%), and the probability of event-free survival (EFS) at 6 years is 0.31 +/- 0.04 (groups A, B, and C: 0.18 +/- 0.05, 0.30 +/- 0.07, and 0.72 +/- 0.11). HDMTX did not prove to be superior to IDMTX, which led to premature stopping of randomization. Risk factor analyses showed early relapse, particularly BM relapse within 18 months, and T-cell phenotype to be independent predictors of poor outcome. The incidence of central nervous system (CNS) relapses following BM relapse was 19%, indicating that reprophylaxis to the CNS with IV/intrathecal (IT) MTX was insufficient. For 17 children who received bone marrow transplantation in second CR from HLA-compatible siblings the EFS was 0.53 +/- 0.12 at 5 years. Their outcome was not influenced by the above-mentioned risk factors. With the proposed treatment regimen long-lasting second remissions can be achieved in about one third of patients even after intensive front- line treatment.

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