This document summarizes guidelines for the management of hematologic emergencies including neutropenic fever, malignant hypercalcemia, and tumor lysis syndrome. It describes the diagnostic criteria and risk factors for these conditions and outlines treatment recommendations. For neutropenic fever it recommends antibiotic regimens, prophylaxis, and use of GCSF. For malignant hypercalcemia it discusses mechanisms and recommends bisphosphonates, denosumab, cinacalcet, or glucocorticoids. For tumor lysis syndrome it emphasizes hydration and recommends allopurinol or rasburicase to lower uric acid levels.

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

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

3. 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

5. 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

6. 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

8. 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

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

10. 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

11. 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

12. 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%

13. 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

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

17. 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

18. 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

19. 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

21. 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

22. 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

23. 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

24. 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

25. 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