Translocation t(8;16)(p11;p13) in neonatal acute monocytic leukaemia

A recent report demonstrated that t(8;16) (p11;p13) may be linked to acute monocytic leukaemia (AMoL) of differentiated subtype (M5b) with active haemophagocytosis by leukaemic cells. Only two cases of neonatal AMoL with t(8;16)(p11;p13) have been reported; M5b with haemophogocytosis and M5a. We report a case of neonatal AMoL (M5b) with t(8;16)(p11;p13), but haemophagocytosis by the leukaemic cells was not detected.     

VP 16–213 and cyclophosphamide in the treatment of refractory acute nonlymphocytic leukemia with monocytic features

The treatment of refractory acute nonlymphocytic leukemia remains a major clinical problem in leukemia therapy. VP 16–213 is an investigational agent that may have specificity for monocytic blasts, and the combination of VP 16–213 and cyclophosphamide is synergistic in experimental leukemia. Seven patients with highly refractory acute nonlymphocytic leukemia, which demonstrated monocytic features, were treated with a combination of VP 16–213 and cyclophosphamide after they had failed to respond to multiple courses of intensive induction regimens. Three complete remissions and one partial remission were achieved. The times to complete remission were 21, 23, and 34 days. The durations of complete remission were 5, 9, and 12+ months. Myelo-suppression was the most common side effect; one patient experienced nausea and stomatitis. There were no documented infections or hemorrhage, and no one died as a result of therapy. This combination is both well tolerated and effective in the treatment of refractory leukemia with monocytic features.     

Translocation t(11;19) (q23;p13) in a child with myelomonocytic leukemia following 2 years after chemotherapy for pneumoblastoma

A child, who received successful chemotherapy for pneumoblastoma, developed a myelomonocytic leukemia with translocation t(11;19)(q23;p13) 2 years later. Although this leukemia did not present with features generally associated with therapy-related leukemias, we think this hematologic disease to be secondary to previous chemotherapy. Involvement of chromosome 11q23 is common in acute leukemia and seems to be more significantly related to ANLL in young children (M4 and M5 FAB classification). However, our observation and previous reports suggest that this chromosomal abnormality might be more frequent in therapy-related leukemias. The responsibility of etoposide and cisplatin may be discussed in such secondary malignancies. © 1993 Wiley-Liss, Inc.     

Successful treatment of a child with T/myeloid acute bilineal leukemia associated with TLX3/BCL11B fusion and 9q deletion

Acute bilineal leukemias are rare and are commonly associated with t(9;22) and MLL abnormalities. Herein, we report a pediatric case of bilineal T/myeloid acute leukemia associated with del (9q)(q13q22) and TLX3/BCL11B fusion due to the cryptic t(5;14)(q35;32). FISH studies confirmed the TLX3/BCL11B fusion in both the myeloid and lymphoid blasts, while the 9q deletion was restricted to the lymphoid component. Optimal therapy for such patients remains controversial and it is not clear if they should be treated with ALL or AML-based chemotherapeutic regimens. Our patient has been in extended remission following ALL-based chemotherapy and a matched unrelated cord blood transplant. Inc.     

Extramedullary leukemia in children with acute myeloid leukemia: A population‐based cohort study from the Nordic Society of Pediatric Hematology and Oncology (NOPHO)

1 Background

The prognostic significance of extramedullary leukemia (EML) in childhood acute myeloid leukemia is not clarified.

2 Procedure

This population‐based study included 315 children from the NOPHO‐AML 2004 trial.

3 Results

At diagnosis, 73 (23%) patients had EML: 39 (12%) had myeloid sarcoma, 22 (7%) had central nervous system disease, and 12 (4%) had both. EML was associated with young age (median age: 2.6 years), a high white blood cell count (median: 40 × 10⁹/l), M5 morphology (40%), and 11q23/MLL (KMT2A) rearrangements (34%). No patient received involved field radiotherapy. Five‐year event‐free survival did not differ significantly between the EML and the non‐EML patients (54% vs. 45%, P = 0.57), whereas 5‐year overall survival (OS) was significantly lower in the EML group (64% vs. 73%, P = 0.04). The risk of induction death was significantly higher for EML patients (8% vs. 1%, P = 0.002). There was a trend toward a lower risk of relapse for EML patients (5‐year cumulative incidence of relapse 33% vs. 49%, P = 0.16). Traumatic lumbar puncture did not adversely affect survival in this cohort.

4 Conclusions

EML was associated with increased risk of induction death impacting the OS. No patients relapsed at the primary site of the myeloid sarcoma despite management without radiotherapy.     

11p15 duplication and 13q34 deletion with Beckwith–Wiedemann syndrome and factor VII deficiency

Here we report a patient with 11p15.4p15.5 duplication and 13q34 deletion presenting with Beckwith–Wiedemann syndrome (BWS) and moderate deficiency of factor VII (FVII). The duplication was initially diagnosed on methylation‐sensitive multiplex ligation‐dependent probe amplification. Array comparative genome hybridization confirmed its presence and indicated a 13q34 distal deletion. The patient's clinical symptoms, including developmental delay and facial dysmorphism, were typical of BWS with paternal 11p15 trisomy. Partial 13q monosomy in this patient is associated with moderate deficiency of FVII and may also overlap with a few symptoms of paternal 11p15 trisomy such as developmental delay and some facial features. To our knowledge this is the first report of 11p15.4p15.5 duplication associated with deletion of 13q34 and FVII deficiency. Moreover, this report emphasizes the importance of detailed clinical as well as molecular examinations in patients with BWS features and developmental delay.     

Translocation t(8;14)(q24;q11) with concurrent PTEN alterations and deletions of STIL/TAL1 and CDKN2A/B in a pediatric case of acute T‐lymphoblastic leukemia: A genetic profile associated with adverse prognosis

We report a pediatric case of acute T‐lymphoblastic leukemia (T‐ALL) with NOTCH1^wt, FBXW7^wt, STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and a minor t(8;14)(q24;q11)‐positive subclone. Undetectable by a flow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by fluorescence in situ hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set of remaining molecular alterations. This case documents an unfavorable prognostic potential of a co‐occurrence of this set of molecular genetic events and addresses risk stratification in T‐ALL.     

Long-term survival in childhood acute leukemia: “Late” relapses

The “late” relapse patterns of childhood acute leukemia were studied in 83 children in their first continuous complete remission for more than three years prior to randomization for stopping therapy (40 patients) or continuing therapy (43 patients) for a total of six years. Twenty of 83 (22.9%) have relapsed: Ten in the bone marrow, one in the central nervous system, and nine in the testes. The testes relapse rate of 41.1% (7/17) in males discontinuing therapy at three years was much higher than that of 8.7% (2/23) in males continuing therapy. This difference is significant at P = 0.01 (Wilcoxon test).     

Facial manifestations of Epstein–Barr virus‐related lymphoproliferative disease in childhood acute lymphoblastic leukemia in remission: Two atypical presentations

Epstein–Barr virus‐related lymphoproliferative disease (EBV‐LPD) rarely occurs in patients with acute lymphoblastic leukemia (ALL), who have not received hematopoietic transplantation. We describe EBV‐LPD manifesting as facial lesions in two children with ALL in remission. One patient was a 16‐year‐old male with T‐cell ALL with an EBV‐positive angiocentric polymorphous lip lesion presenting as right‐sided facial swelling. The other patient was a 12‐year‐old male with B‐cell ALL with an EBV‐positive polymorphous lymphoplasmacytic infiltrate presenting as bilateral dacryoadenitis. Neither patient had known primary immunodeficiencies. Both cases improved with immunosuppressant de‐escalation. These cases suggest that immunosuppression induced by maintenance chemotherapy is sufficient to promote EBV‐LPD.