CASE PRESENTATION
A 30 year-old male with Down syndrome presented with fever, cough, and
shortness of breath in November 2013. He was managed in our pediatric
unit because of current favorable outcomes for Adolescents and Young
Adults (AYA) with ALL treating with pediatric COG
protocols.11 His complete blood count (CBC) showed
pancytopenia with a white blood cell (WBC) count of 1.4 x 10^9/L,
hemoglobin of 8.3 g/dL, and platelet count of 32 x 10^9/L with
occasional circulating blasts. Bone marrow aspirate and biopsy confirmed
the diagnosis of acute lymphoblastic leukemia with 73% blasts which
co-expressed CD34, CD19, CD10 and TdT with aberrant expression of dim
CD33 by flow cytometry, which was consistent with B-precursor ALL.
Cytogenetic analysis was not successful but FISH from a bone marrow
sample obtained on day 17 during Induction chemotherapy as per the
Children’s Oncology Group (COG) study AALL1131 showed nuc
ish(ETV6x2,RUNX1x3)[250] which was a normal signal pattern for
constitutional trisomy 21 with two ETV6 signals and three RUNX1 signals.
Diagnostic cerebrospinal fluid was negative for blasts.
The patient was treated per COG high risk protocol AALL1131, Down
syndrome arm due to NCI risk factor for age above 10 years old. He had a
rapid early response with a M1 marrow at Day 17 and he achieved complete
remission after Induction with negative minimal residual disease (MRD).
He had a complicated treatment course including a few episodes of
sepsis, one of which included multi-organ failure for which he was in
the Medical ICU, and PICC line associated DVT, Following the end of his
treatment, his platelet count never normalized and ranged between
90x10^9/L and 112x10^9/L. At his lowest level of thrombocytopenia
to 48x10^9/L in September 2017, which was four years after the
initial diagnosis, a repeat bone marrow aspirate and biopsy was obtained
and showed a 90% cellular bone marrow with 82% blasts, consistent with
late bone marrow relapse. FISH showed CRLF2 translocation positive in
63.5% of cells and was also positive for deletion of CDKN2A on
chromosome 9p beside his constitutional trisomy of chromosome 21. CNS
was negative. This relapse was treated with Reinduction chemotherapy per
ALL R3 protocol (Dexamethasone 20mg/m2/day day 1-5 & 15-19,
Mitoxantrone 10mg/m2/dose day 1-2, Vincristine 1.5mg/m2/dose from day 3,
then weekly; PEG-asparaginase 2500U/M2 day 3 and 18; Intrathecal
Methotrexate day 1 and 8). Post-reinduction day 29 MRD was 0.2% (Table
1).
He continued to receive Consolidation chemotherapy per ALL R3 protocol
(Intrathecal Methotrexate day 1, Dexamethasone 6mg/m2/day day 1-5,
methotrexate 1000mg/m2/dose day 8 with Leucovorin rescue, Vincristine
1.5ng/m2/dose day 3, PEG-asparaginase 2500U/m2/dose day 9,
Cyclophosphamide 440mg/m2/dose day 15-19, Etoposide 100mg/m2/dose day
15-19), after which his bone marrow had negative MRD. While hospitalized
for Intensification chemotherapy, he developed sepsis, necrotizing
pneumonia, and severe bilateral pleural effusions. BAL revealed Candida
albicans. CT imaging also revealed near complete splenic infarct, right
renal perfusion deficits with signs of liquefaction and a segmental area
of abnormal small bowel wall enhancement and concern for focal small
bowel wall defect. He also developed delirium related to his severe
illness and prolonged hospitalization. Due to severe illness, his
chemotherapy was held during a three month period. A bone marrow after
three months continued to demonstrate negative MRD. Once he became more
clinically stable, chemotherapy was attempted with intermediate dosed
Methotrexate but this hospital course was complicated by infection
necessitating removal of his broviac, fluid overload, and a persistent
cavitary lung lesion. At this point, a decision was made by his family
and treatment team to stop chemotherapy. About 50 weeks after his
diagnosis of relapsed disease, a repeat bone marrow continued to
demonstrate negative MRD. He was followed closely as an outpatient.
Unfortunately, he presented with acute onset psychosis and
thrombocytopenia about 2 years after stopping his treatment and bone
marrow was consistent with relapsed disease. Family opted for no further
therapy and unfortunately the patient passed away 7 weeks later.