White Cell Disorders

Question 1

What are the clinical features of chronic granulomatous disease and what is the enzyme defect?

Answer 1

Recurrent skin and lung infections. The enzyme defect is NADPH oxidase deficiency.

Question 2

What is the mode of inheritance of chronic granulomatous disease?

Answer 2

Mostly autosomal recessive, but some can be X-linked.

Question 3

How do you treat chronic granulomatous disease?

Answer 3

You give these patients Bactrim and Itraconazole for prophylaxis. Can consider interferon gamma, BMT, and gene therapy.

Question 4

What are the clinical features of MPO deficiency?

Answer 4

Most patients are asymptomatic, however in those with uncontrolled diabetes the symptoms may be unmasked.

Question 5

How do you make the diagnosis of MPO deficiency?

Answer 5

By histochemical staining for MPO

Question 6

What are the clinical features of Hyper IgE syndrome?

Answer 6

These patients develop skin, lung, sinus infections (often yeast)

Question 7

What gene is affected in Hyper IgE syndrome?

Answer 7

STAT3 gene.

Question 8

How do you diagnose chronic granulomatous disease?

Answer 8

Diagnosis is with nitroblue-tetrazolium reduction (cytochrome C reduction assay)

Question 9

What are the clinical features of Chediak Higashi Syndrome?

Answer 9

oculocutaneous albinism ,photophobia, mild neutropenia, neurologic defects (e.g. neuropathy), recurrent pyogenic infections, bleeding (dense platelet granule defect).

Question 10

What is the mode of inheritance of Chediak Higahsi and what is the gene mutation?

Answer 10

Autosomal recessive and the gene affected is LYST gene

Question 11

What is the treatment of Chediak Higahsi Syndrome?

Answer 11

BMT

Question 12

In cyclical neutropenia what is the mode of inheritance and what gene is involved?

Answer 12

Autosomal dominant and it’s the ELANE gene.

Question 13

What is the major complication that can occur later in life with severe congenital neutropenia? What has been associated with this?

Answer 13

AML. It appears the longer patients are on G-CSF the higher risk is with this occurring.

Question 14

What somatic mutation occurs with G-CSF that increases the risk of AML in patients with severe congenital neutropenia?

Answer 14

CSF3R mutation

Question 15

What is the treatment of both congenital neutropenia and cyclical neutropenia?

Answer 15

G-CSF

Question 16

What is the treatment of congenital neutropenia refractory to treatment?

Answer 16

BMT

Question 17

What are the clinical features of WHIM?

Answer 17

Warts, hypogammaglobulinemia, infections, and myelokathexis (increased marrow mature neutrophils).

Question 18

What genetic mutation characterizes WHIM? What is the result of this mutation?

Answer 18

There is a mutation involves the CXCR4 gene. Mutations result in enhanced retention of neutrophils in the bone marrow

Question 19

What is the treatment of WHIM syndrome?

Answer 19

IVIG, prophylactic antibiotics, and Plerixafor.

Question 20

What mutation is commonly seen in Langerhans Cell Histiocytosis?

Answer 20

Over 70% of cases have a somatic mutation in BRAF.

Question 21

What is the treatment of SS-LCH involving the bone?

Answer 21

Bony or soft tissue SS-LCH can be treated with surgical resection, local irradiation, or injection of steroids. NCCN lists Zoledronic Acid and Pamidronate-systemic tx for widespread disease.

Question 22

What is the treatment of skin SS-LCH?

Answer 22

topical steroids or injection, mechlorethamine topical, or psoralen and ultraviolet A light therapy, RT low dose. NCCN-MTX, hydrea (both preferred), Lenalidomide, Thalidomide-additional, but not preferred

Question 23

What is the treatment of lung SS-LCH?

Answer 23

Cessation of smoking, prednisone, vinblastine, and methotrexate; and immunosuppressive agents. NCCN: basically the systemic options you use for multi-system disease.

Question 24

What is the tx of MS-LCH and SS-LCH with multi-focal involvement?

Answer 24

Preferred: Cladribine or Cytarabine. MAP kinase mutation or no actionable mutation-Cobimetinib. Vinblastine and prednisone is another option.. Those with BRAF mutation you use Vemurafenib (preferred) or Dabrafenib.

Question 25

What is flow cytometry result for Erdheim Chester Disease?

Answer 25

Positive for CD163 and CD68, CD14, but are negative for CD1a and langerin (CD207, unlike in LCH), and only rarely positive for S100.

Question 26

What is the treatment of Erdheim Chester Disease?

Answer 26

NCCN: Vemurafenib (preferred) or dabrafenib for BRAF mutation. MAP kinase mutation or no detectable mutation: Cobimetinib (preferred) or Trametinib. Irrespective of mutation, other recs: Cladribine, Peg Interferon alpha, Sirolimis plus prednisone, MTX, Anakinra

Question 27

What is the flow phenotype of LGL?

Answer 27

CD3+, CD16+, CD57+, CD28-

Question 28

What is the flow phenotype for LCH?

Answer 28

CD1a, CD207 (Langerin), S100+, Cyclin D1+