Acute Myeloid Leukaemia after Treatment for Acute Lymphoblastic Leukaemia in Girl with Bloom Syndrome

Abstract

Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress.

Single‐center pediatric experience with venetoclax and azacitidine as treatment for myelodysplastic syndrome and acute myeloid leukemia

“…The two nonresponders had congenital KMT2A ‐rearranged ALL with lineage switch after CAR‐T therapy and AML as a second malignancy in the setting of a DNA damage repair defect, respectively. In the literature, AML in patients with Bloom syndrome is uniformly fatal 20‐23 from either therapy‐related hypertoxicity or refractory disease.…”

Multidisciplinary management of endocrinopathies and treatment‐related toxicities in patients with Bloom syndrome and cancer

“…[14][15][16][17] Others received various dose modifications and reductions, which in most cases reduced toxicity, and in some successfully induced remission. [18][19][20][21][22] We report on two patients with BS who were treated for leukemia with markedly reduced intensity regimens and achieved remission, one of whom with a disease-free survival of currently greater than 11 years. Based on our experience with these patients, we propose several principles to consider when designing a treatment regimen.…”

“…Many patients with BS who were treated with standard chemotherapy suffered significant or fatal toxicities 14–17 . Others received various dose modifications and reductions, which in most cases reduced toxicity, and in some successfully induced remission 18–22 . We report on two patients with BS who were treated for leukemia with markedly reduced intensity regimens and achieved remission, one of whom with a disease‐free survival of currently greater than 11 years.…”

Childhood cancer predisposition syndromes—A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology

“…The frequency of TP53 germline mutations is increased in children with relapses of ALL (Hof et al, ). ALL is also diagnosed in the context of DNA repair disorders such as ataxia telangiectasia ( ATM , gene product is crucial for DNA damage repair; MIM 208900) (Schoenaker, Suarez, Szczepanski, Mahlaoui, & Loeffen, ), Bloom syndrome ( BLM , coding for DNA helicase involved in recombination; MIM 210900) (Adams et al, ), or Fanconi anemia ( FANCA‐V , MIM 607139, 300515, 613899, 600185, 613984, 613976, 603467, 614082, 611360, 609054, 614083, 609644, 610832, 613390, 631951, 615272, 179617, 113705, 616435, 600375, 604094; encoding for proteins of multi‐subunit nuclear complexes controlling DNA repair) (Svojgr et al, ). T‐cell ALL has been described in children with constitutional mismatch repair deficiency syndrome ( MLH1 , MSH2 , MSH6 , PMS2 ; CMMRD, MIM 276300) (Ripperger & Schlegelberger, ) and biallelic mutations in BRCA2 ( FANCD1 , MIM 600185) (Wagner et al, ).…”