ABSTRACT
The patient reported here underwent hematopoietic stem cell transplantation (HSCT) due to chronic granulomatous disease (CGD) caused by biallelic mutations of the NCF1 gene. Two years later, he developed AML, which was unexpected and was recognized via sex-mismatched chromosomes as deriving from the donor cells; the patient was male, and the donor was his sister. Donor cell leukemia (DCL) is very rare, and it had never been reported in patients with CGD after HSCT. In the subsequent ten years, the AML relapsed three times and the patient underwent chemotherapy and three further HSCTs; donors were the same sister from the first HSCT, an unrelated donor, and his mother. The patient died during the third relapse. The DCL was characterized since onset by an acquired translocation between chromosomes 9 and 11, with a molecular rearrangement between the MLL and MLLT3 genes-a quite frequent cause of AML. In all of the relapses, the malignant clone had XX sex chromosomes and this rearrangement, thus indicating that it was always the original clone derived from the transplanted sister's cells. It exhibited the ability to remain quiescent in the BM during repeated chemotherapy courses, remission periods and HSCT. The leukemic clone then acquired different additional anomalies during the ten years of follow-up, with cytogenetic results characterized both by anomalies frequent in AML and by different, non-recurrent changes. This type of cytogenetic course is uncommon in AML.
Subject(s)
Granulomatous Disease, Chronic , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Male , Granulomatous Disease, Chronic/genetics , Granulomatous Disease, Chronic/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Unrelated Donors , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/pathology , Translocation, GeneticSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Flow Cytometry , Neoplasm, Residual/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Marrow/pathology , Female , Flow Cytometry/methods , Humans , Incidence , Infant , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Recurrence , Survival Analysis , Treatment OutcomeABSTRACT
A twin pair affected by juvenile myelomonocytic leukemia (JMML) with the same somatic PTPN11 mutation and abnormal chromosome 7 in bone marrow samples but distinct prognostic gene expression signatures, received a matched-unrelated donor and matched-unrelated cord blood transplant, respectively. Both twins fully engrafted, but after 6 months, the twin with an acute-myeloid-like (AML-like) signature at diagnosis rejected the graft and had an autologous reconstitution. A second transplant with an unrelated 5/6-HLA-matched-loci cord blood performed after 4 months from rejection was unsuccessful. After 25 months from diagnosis, the twin with the AML-like gene expression signature died of liver failure while on progression of his JMML. The other twin, who had a non-acute-myeloid-like (non-AML-like) gene expression signature at diagnosis is in complete hematological remission with full donor chimera. This observation suggests a biological diversity of JMML also in patients with a common genetic background.
Subject(s)
Diseases in Twins/therapy , Graft Rejection/physiopathology , Graft Survival , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myelomonocytic, Juvenile/therapy , Cord Blood Stem Cell Transplantation/adverse effects , Diseases in Twins/diagnosis , Diseases in Twins/immunology , Diseases in Twins/metabolism , Fatal Outcome , Gene Expression Profiling , Gene Expression Regulation, Leukemic , Graft Rejection/immunology , Humans , Infant , Leukemia, Myelomonocytic, Juvenile/diagnosis , Leukemia, Myelomonocytic, Juvenile/immunology , Leukemia, Myelomonocytic, Juvenile/metabolism , Male , Prognosis , Remission Induction , Transplantation, Homologous , Treatment Outcome , Twins, MonozygoticABSTRACT
BACKGROUND: Anaplastic large cell lymphoma (ALCL) constitutes approximately 15% of pediatric and 3% of adult non-Hodgkin lymphomas. Most pediatric cases harbor the reciprocal translocation t(2;5)(p23;q35), involving the alk gene. Cytogenetic studies of ALCL have mostly been published as case-reports. The aim of this study was to determine the cytogenetic profiles of a series of pediatric ALCL and to compare them with pediatric and adult ALCL from the literature. METHODS: Eighteen children treated at our Institution were studied by standard cytogenetic analysis and RT-PCR for the specific t(2;5) translocation product. Comparative analysis was performed on our findings and on the karyotypes of 48 pediatric and 39 adult ALCL reported in the literature. RESULTS: Karyotype was obtained in 16/18 ALCL: 9 showed translocation t(2;5) and 1 an alk variant form. Structural and numeric chromosomal abnormalities were identified in both pediatric and adult series. Trisomies were found preferentially in pediatric patients (P = 0.013) and monosomies in adults (P = 0.038). Trisomy 7 was found in 22% (13/59) of pediatric cases with abnormal karyotype and only in 5% (2/38) of adults; monosomy of chromosome 13 in 13% (5/38) of adults and only in 2% (1/59) of pediatric patients and monosomy of chromosome 15 in 16% (6/38) of adults and in none of the pediatric ALCL. CONCLUSION: Our data suggest that pediatric and adult ALCL are characterized by different numerical chromosomal abnormalities. Larger prospective studies may elucidate their potential prognostic impact.
