Acute Lymphoblastic Supportive Care in Pediatric Oncology irantextbook.ir 93df
≥ 200 × 10
9
L Möricke et al. 2008
; Gaynon et al. 2010
; Lund et al. 2011
. For the 132 patients with initial WBC ≥200 × 10
9
L in the Scandinavian NOPHO ALL-92 and ALL-2000 protocols,
7 5.3 suffered early death, 6 secondary to neurologic complications, and none secondary
to TLS with 5 dying prior to therapy initiation Lund et al.
2011 .
Table 6.1
Summary of management strategies and level of evidence for management of pediatric leukemic hyperleukocytosis
a
Disease Potential side
effect Treatment
Level of evidence
b
Acute lymphoblastic
leukemia Leukostasis
Rapid initiation of chemotherapy 1A
Hyperhydration 1C
Consider leukapheresis for WBC 400–600 × 10
9
L if no delay in antileukemic chemotherapy initiation
2C Tumor lysis
syndrome Hyperhydration
1B One dose of rasburicase prior to antileukemic chemotherapy
initiation; see Chap. 3
for more detail 1A
Isolated hyperuricemia
One dose of prophylactic rasburicase 1B
Follow with alkalinization and allopurinol 2C
Consider additional rasburicase doses if repeat uric acid 7.5 mgdL 2C DICcoagulopathy FFP to keep PTPTT WNL
1C Fibrinogen concentrate or cryo to keep fi brinogen 150 mgdL
1C Thrombocytopenia Platelet transfusion to keep platelets 50 × 10
9
L if WBC 300–400 × 10
9
L 1C
Symptomatic anemia
Transfuse small aliquots e.g., 5 mLkg and keep hgb 10 gdL 1C
Acute myelogenous
leukemia except APL
Leukostasis Rapid initiation of chemotherapy
1A Careful hydration
1C Consider leukapheresis
2C Consider HU
2C Tumor lysis
syndrome Hyperhydration
1C One dose of rasburicase if uric acid 7.5 mgdL; see Chap.
3 for
more detail 2C
DICcoagulopathy FFP to keep PTPTT WNL 1C
Fibrinogen concentrate or cryo to keep fi brinogen 150 mgdL 1C
Thrombocytopenia Platelet transfusion to keep platelets 50 × 10
9
L 1C
Isolated hyperuricemia
One dose of prophylactic rasburicase 1B
Follow with alkalinization and allopurinol 2C
Consider additional rasburicase doses if repeat uric acid 7.5 mgdL 2C Symptomatic
anemia Transfuse small aliquots e.g., 5 mLkg and keep hgb 10 gdL
1C Acute
promyelocytic leukemia
DICcoagulopathy Rapid initiation of ATRA or ATO 1A
FFP to keep PTPTT WNL 1C
Fibrinogen concentrate or cryo to keep fi brinogen 150 mgdL 1C
Avoid invasive procedures 1C
Unclear benefi t of leukapheresis 2C
Thrombocytopenia Platelet transfusion to keep platelets 50 × 10
9
L at the minimum 1C
APL differentiation syndromeRAS
Dexamethasone 1B
Leukocytosis with ATRA or ATO
HU 1B
Consider holding ATRA or ATO 1C
continued 6 Hyperleukocytosis
In a follow-up study of 221 NOPHO patients with WBC ≥200 × 10
9
L, Vaitkevičienė et al. 2013
importantly note that all complications sec- ondary to HL, except the need for dialysis,
occurred at signifi cantly higher median WBC counts: neurologic WBC 530
× 10
9
L vs.
327 × 10
9
L, respiratory WBC 620 × 10
9
L vs. 336 × 10
9
L, bleeding WBC 420 ×
10
9
L vs. 327 × 10
9
L, and dialysis WBC 310 × 10
9
L vs. 357 × 10
9
L. Neurologic and bleeding complica- tions occurred at a signifi cantly higher age, while
respiratory distress occurred at a signifi cantly younger age. In multivariate analysis, only WBC
count and neurologic symptoms at admission were signifi cantly associated with risk of early death;
timing of administration of antileukemic therapy, admission hemoglobin level and administration of
packed red blood cells PRBCs were not signifi - cant. Six patients 2.7 died within 2 weeks of
presentation, all secondary to neurologic compli- cations, with 4 of the 6 presenting with severe
symptoms. Patients receiving mechanical cytore- duction leukapheresis or exchange transfusion
prior to chemotherapy initiation had signifi cant delay in antileukemic therapy initiation with no
noted survival benefi t. TLS occurred in 12 of patients with statistically higher initial uric acid
levels 11.0 vs. 7.7 mgdL. Patients with T-cell and infant ALL were at increased risk of TLS, ras-
buricase signifi cantly reduced the risk of TLS and no patient died from TLS. Initial uric acid level
was the only signifi cant factor for the development of TLS on multivariate analysis WBC count, lac-
tate dehydrogenase, corticosteroid dose and mechanical cytoreduction were not signifi cant. In
their supplemental HL guidelines, Vaitkevičienė et al.
2013 recommend prompt initiation of anti-
leukemic therapy after diagnostic evaluations and rasburicase administration with no recommenda-
tion for leukapheresis or exchange transfusion. Maurer et al.
1988 similarly reported an
8.4 incidence of WBC 200 × 10
9
L in a pedi- atric ALL cohort. Early death occurred in 7 of
124 5.6 patients, 4 from sepsis, 1 from pneumonia, 1 from GI hemorrhage and 1 from
ICH. Four 3.2 patients suffered ICH with 3 occurring at presentation and all with WBC
600 × 10
9
L. Although electrolyte abnormali- ties were decreased in those undergoing leuka-
pheresis, risk of renal dysfunction requiring dialysis was low, occurring in only 3 2.4
patients, all of whom had received low-dose prednisone pretreatment. WBC 600
× 10
9
L and massive splenomegaly were the only sig-
nifi cant adverse prognostic factors on multivari- ate analysis.
In a comprehensive study of HL over a 40-year period at St. Jude Children’s Research
Hospital, Lowe et al. 2005
reported 178 of 2,288 7.8 children with ALL presenting with
WBC 200 × 10
9
L. Early death occurred in 7 3.9 , 3 from sepsis and 2 each from ICH and
Disease Potential side
effect Treatment
Level of evidence
b
Chronic myelogenous
leukemia Leukostasis
Hyperhydration 1C
HU 1C
Consider leukapheresis 2C
Priapism Hyperhydration
1C HU
1C Consider leukapheresis
2C Urologic consultation for therapeutic aspiration and possible
intracavernous sympathomimetic therapy 1C
Pain management 1C
WBC white blood cell, DIC disseminated intravascular coagulation, FFP fresh frozen plasma, PT prothrombin time, PTT partial thromboplastin time, WNL within normal limits, cryo cryoprecipitate, hgb hemoglobin, APL acute promy-
elocytic leukemia, HU hydroxyurea, RAS retinoic acid syndrome, ATRA all-trans retinoic acid, ATO arsenic trioxide
a
See text for full detail
b
Per Guyatt et al. 2006
; see Preface
Table 6.1
continued A.E. Aguilar et al.
respiratory failure. Cytoreduction was performed in those with a median initial leukocyte count of
416 × 10
9
L vs. 295 × 10
9
L in the nonreduced cohort. The time to initiate chemotherapy was
signifi cantly longer in the cytoreduced cohort. Neurologic and respiratory complications were
statistically more likely with WBC 400 × 10
9
L. Older age was also signifi cant for neurologic
complications. Four patients suffered from ICH 2.2 , all with initial WBC 400 × 10
9
L and 3 at initial presentation to the tertiary care institu-
tion. Two of the 4 received PRBC transfusion prior to ICH, while the other 2 had initial hemo-
globin of 10.1 and 10.2 gdL. The majority of neurologic complications 13 of 16; 81
occurred at presentation; the additional 3 occurred 24 h after presentation, 1 in the cytore-
duced group and 2 in the nonreduced cohort. Pulmonary complications occurred more com-
monly in the cytoreduced cohort and were equally common before and after cytoreduction.
Metabolic complications were common, with hyperkalemia in 10 and hyperphosphatemia in
20 , but only 1 patient died secondary to meta- bolic dysfunction hyperkalemia and overt renal
dysfunction was rare. Although it was unclear if cytoreduction was benefi cial in the prevention of
TLS or leukostasis symptoms and did not impact early mortality, Lowe et al.
2005 recommend
cytoreduction for WBC 400 × 10
9
L. Again, early initiation of chemotherapy in pediatric
ALL seems most important although it is unlikely to impact those presenting with severe
neurologic dysfunction and may not impact early death.