Hematologic Emergencies
By: Esteban Toro Vélez, MD
Internal Medicine Resident, UTHSCSA
PGY-2

Neutropenic Fever
● ANC less than 500
○ Less than 1000 and expecting a drop in next 48h
○ Profound: Less than 100
● Fever: 38.3 once or 38 for more than an hour
● Infectious etiology identified in 40-50% of cases
○ Bacteremia 10-30%
● Mortality rate of up to 70% if no empiric antibiotics

Risk Assessment and Evaluation
● 2 sets of blood cultures
(peripheral and central if
available)
● Type of chemotherapy, cycles of
chemotherapy
● Prior infections, prophylaxis
● Exposures
● Detailed physical exam: Skin,
perirectal area
● Dedicated imaging
● MASCC

https://www.uptodate.com/contents/treatment-of-neutropenic-fever-syndromes-in-adults-with-hematologic-malignancies-and-hematopoietic-cell-transplant-recipients-high-risk-
patients?search=neutropenic%20fever&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2

https://www.uptodate.com/contents/treatment-of-neutropenic-fever-syndromes-in-adults-with-hematologic-malignancies-and-hematopoietic-cell-transplant-recipients-high-risk-
patients?search=neutropenic%20fever&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2

Antibiotics
● Ensure antipseudomonal coverage
● Add agents if complications or
resistance
● Vancomycin
○ Not recommended as initial regimen
○ Catheter related, skin and soft tissue
infection, pneumonia
○ Stop 48h after if no Gram+
● Antifungals if prolonged
neutropenia
1. Appropriate length of duration +
ANC above 500
2. ANC above 500 and afebrile
3. If infection has resolved, ANC
below 500, could resume
prophylaxis

Prophylaxis
https://www.nccn.org/professionals/physician_gls/pdf/infections.pdf

Bacterial
● Intermediate to high
risk patients
● Consider
fluoroquinolone
prophylaxis during
neutropenia period
Fungal Viral PJP
● ALL, autologous/
allogeneic HCT with
mucositis→fluconaz
ole or echinocandin
● MDL/AML→posaco
nazole
● HSV seropositive
patients
undergoing HSCT
or leukemia
induction
● Acyvlovir and
valacyclovir Until
recovery of WBC
or resolution of
mucositis
● VZV prophylaxis if
proteasome
inhibitors,
alemtuzumab,
allogenic or GVHD
● Allogeneic HCT,
ALL, prolonged
course of steroids,
Alemtuzumab,
idelasib,
temozolomide,
fludarabine,
cladribine
● TMP/SMX,
Dapsone,
aerosolized
pentamidine
https://www.nccn.org/professionals/physician_gls/pdf/infections.pdf

GCSF
● Sepsis
● Age > 65 years old
● Pneumonia or other documented infection
● Invasive fungal infection
● ANC < 100 K/microliter
● Expected neutropenia duration > 10 days
● Hospitalization at the time of fever or prior episode of neutropenic fever
https://www.mdanderson.org/content/dam/mdanderson/documents/for-physicians/algorithms/clinical-management/clin-management-neutropenic-fever-inpt-heme-web-
algorithm.pdf

Malignant Hypercalcemia
● Up to 30% of patients with cancer
● Risk depends of type and stage
○ Lung cancer
○ Multiple myeloma
○ Renal cell
○ Breast
○ Colon
○ Prostate
● 30 day mortality up to 50%

Symptoms
● Depend on acuity and level of calcium
● Mild
○ Asymptomatic or nonspecific
○ Lethargy, MSK pain
● Severe or rapid change
○ Volume depletion, acute kidney injury
○ Neurocognitive: AMS to coma

Proposed Mechanisms
● Humoral hypercalcemia mediate by
PTHrP
● Local osteolytic hypercalcemia
● Excess extrarenal activated
Vitamin-D
● PTH secretion, ectopic or primary,
others

Bisphosphonates
● Osteoclast apoptosis and osteoblast
differentiation
● 2-4 days for effect
● Zoledronic acid 4mg IV
○ Ok if creatinine less than 4.5
○ Repeat after 7 days
○ Renal dose adjustment
● Pamidronate 60-90mg IV
● Targets RANKL
● Hypercalcemia refractory
bisphosphonates
● 120mg sc on days 1, 8, 15 and 29
then 4 weeks thereafter
● 60mg SC once
Denosumab

Cinacalcet
● Can be used with bisphosphonates
● Tachyphylaxis occur within 48h
● Inhibit osteoclastic bone
resorption
● Hydrocortisone 200-400mg for 3-
4 days. Followed by 10-20mg of
prednisone for 7 days
● Prednisone 40=60mg for 10 days
Glucocorticoids

Tumor Lysis Syndrome
● Most frequent in hematologic malignancies
● Can occur spontaneously
● High proliferative rate, large tumors, sensitivity to treatment
● Release of metabolites leading to
○ Hyperuricemia
○ Hyperkalemia
○ Hyperphosphatemia
○ Hypocalcemia
○ Uremia
Coiffier B, Altman A, Pui C-H, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor lysis syndrome: An evidence-based review. Journal of Clinical Oncology

Coiffier B, Altman A, Pui C-H, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor lysis syndrome: An evidence-based review. Journal of Clinical Oncology

Coiffier B, Altman A, Pui C-H, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor lysis syndrome: An evidence-based review. Journal of Clinical Oncology

Coiffier B, Altman A, Pui C-H, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor lysis syndrome: An evidence-based review. Journal of Clinical Oncology

Treatment
1. Hydration is the cornerstone
a. Urine output of 80-100ml/m2/h
2. No need for alkalinization
a. Historical
b. Increases calcium pyrophosphate
deposition
3. Urate lowering therapies
a. Allopurinol and rasburicase
Coiffier B, Altman A, Pui C-H, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor lysis syndrome: An evidence-based review. Journal of Clinical

Allopurinol
● For intermediate risk patients
● Start 1-2 days before chemo, and up to 3-
7 days post chemo
● Continue until normal uric acid, decreased
WBC and normal TLS labs
● If preexistent hyperuricemia, rasburicase
is preferred
● Dose
○ PO, maximum of 800mg/day
○ IV, maximum of 600mg/day
● For high risk patients or moderate with
hyperuricemia
● Contraindicated in G6PD deficiency
● 0.1-0.2mg/kg/day, up to 7 days
Rasburicase
https://www.mdanderson.org/content/dam/mdanderson/documents/for-physicians/algorithms/clinical-management/clin-management-neutropenic-fever-inpt-heme-web-algorithm.pdf