Promising therapy results for lymphoid malignancies in children with chromosomal breakage syndromes (Ataxia teleangiectasia or Nijmegen‐breakage syndrome): a retrospective survey

Abstract

Summary Children with chromosomal instability syndromes have an increased risk of developing lymphoma and leukaemia. The treatment of these malignancies is hampered by therapy‐associated toxicity and infectious complications. This retrospective analysis evaluated the therapy outcome of 38 children with Ataxia teleangiectasia or Nijmegen‐breakage syndrome with acute lymphoblastic leukaemia (ALL, n = 9), Non‐Hodgkin lymphoma (NHL, n = 28) and Hodgkin lymphoma (HL, n = 1). All patients with NHL or ALL were treated in accordance to Berlin‐Frankfurt‐Münster (BFM)‐ or Co‐operative study group for childhood ALL (CoALL)‐oriented chemotherapy schedules. 22 patients received significantly reduced‐intensity chemotherapy. After a median follow‐up of 3·7 years the 10‐year overall survival was 58%. Dosage‐reduction of chemotherapeutic drugs seemed to have no disadvantages and reduced toxic side effects. On the other hand, reduced‐intensity chemotherapy did not prevent second malignancies, which occurred in ten patients with a 10‐year incidence of 25%. After individual treatment approaches three of these patients with second malignancies were in complete clinical remission for more than 5 years. We conclude that BFM‐ or CoALL‐oriented chemotherapy is effective and can be administered in children with AT or NBS. Moreover, we show that even second lymphoid malignancies can successfully be treated in these patients.

Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents

“…[5][6][7][8]10,16,22,46 Our analysis showed that while approximately 50% of AT patients died from therapy-related toxicity, death from NHL and therapy-related complications was evenly distributed among NBS patients. In comparison, the NHL-BFM SG reported on 37 patients with chromosomal instability syndromes (AT and NBS) with 5-year EFS rates of 48%±12% for 16 patients with ALL/T-LBL (relapse/progression n=2; SML n=2; treatment-related death n=2; alive n=10) and 51%±16% for 21 patients with mature B-cell NHL (relapse/progression n=2; SML n=2; treatment-related death n=1; dead from underlying disorder n=4; alive n=12).…”

“…In comparison, the NHL-BFM SG reported on 37 patients with chromosomal instability syndromes (AT and NBS) with 5-year EFS rates of 48%±12% for 16 patients with ALL/T-LBL (relapse/progression n=2; SML n=2; treatment-related death n=2; alive n=10) and 51%±16% for 21 patients with mature B-cell NHL (relapse/progression n=2; SML n=2; treatment-related death n=1; dead from underlying disorder n=4; alive n=12). 6 Of our CMMRD patients, nearly 75% died, either from NHL or another SML. This extremely high mortality rate also confirms that CMMRD has to be diagnosed in a timely fashion to allow tumor surveillance, and that adapted chemotherapies are necessary to treat the different highly resistant childhood cancers occurring in this group of patients.…”

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Primary immunodeficiencies (PID) such as DNA repair defects (Nijmegen breakage syndrome, Ataxia telangiectasia, Bloom syndrome or constitutional mismatch repair deficiency), severe combined immunodeficiencies (SCID), common variable immunodeficiencies (CVID), and immune-osseous dysplasias (Di George syndrome or cartilage hair hypoplasia) have an extraordinary risk of developing leukemia and lymphoma. [5][6][7][8][9][10][11][12][13][14][15][16][17]20,21 Although these patients seem to have an inferior prognosis and an increased risk of treatment-related toxicity and death compared to patients with lymphoid malignancies without a PID, curative therapies including allogeneic stem cell transplantation (allo-SCT) have been repeatedly reported. 5,6,10,11,15,16,22 Systematic data on the spectrum of common and rare pre-existing conditions associated with NHL in children and adolescents are scarce with respect to the type of the pre-existing conditions and the clinical characteristics and outcome of the associated NHL subtypes.…”

“…[5][6][7][8][9][10][11][12][13][14][15][16][17]20,21 Although these patients seem to have an inferior prognosis and an increased risk of treatment-related toxicity and death compared to patients with lymphoid malignancies without a PID, curative therapies including allogeneic stem cell transplantation (allo-SCT) have been repeatedly reported. 5,6,10,11,15,16,22 Systematic data on the spectrum of common and rare pre-existing conditions associated with NHL in children and adolescents are scarce with respect to the type of the pre-existing conditions and the clinical characteristics and outcome of the associated NHL subtypes. Thus, the two largest childhood NHL consortia, the European Intergroup for Childhood NHL (EICNHL) and the international Berlin-Frankfurt-Münster (i-BFM) Study Group (SG), designed a retrospective multinational study to collect data on unselected types of pre-existing conditions among children and adolescents with NHL.…”

Molecular Origin of Childhood Acute Lymphoblastic Leukemia

“…Children with ALL have a 5-year survival rate of more than 90 % (Bienemann et al 2011 ). It may well be that a proportion of the 10 % of children who do not survive are enriched for children with cancer-predisposing conditions that make them prone for comorbidity, second primary malignancies, and more severe toxic side effects of treatment.…”