[CIS PIDD] [cis-pidd] Cartilage Hair Hypoplasia Management

Thu Jan 21 14:27:28 EST 2016

Dear Jordan,

We have a patient of Amish origin with the founder mutation RMRP 70A>G who also got picked up on NBS for whom we recommended transplant. His CD4 T-cells at diagnosis was 250-300 with CD4 naive T cells of 6-9% . Mitogen proliferation was decreased (PHA responses ranged between 14000-40000). Absent TRECs at 3 months. Normal B and NK cells and no cytopenias. Family was on board with transplant as they knew another amish family whose child with CHH/SCID had significant complications from SCID. The more difficult decision was whether to proceed with unconditioned or conditioned prep as we had a matched sibling donor. We gave the family both options:
(1) BMT with no conditioning which would avoid risks/toxicities associated with chemotherapy in early half of infancy but with the understanding that if not successful or if immune reconstitution is inadequate, will later need a conditioned BMT.
(2) Delay BMT until older (6 months) and proceed with BMT with reduced intensity conditioning -campath/flu/mel (realizing risk of infection with delay).
We started the pt on PCP prophylaxis and IVIG at diagnosis. Family eventually preferred an unconditioned BMT and pt received an unmodified marrow graft from his sibling (no GVH prophylaxis) around 5 months of age. He had an uneventful course except for CMV viremia. Is now >15 months post BMT with adequate T-cell reconstitution (CD4 T cells 950, CD4 naive T cells 40% and normal mitogen responses. Recently taken off IVIG. At 15months, donor engraftment 84% in T cells, 48% in NK cells, 26% in B-cells and 2% in myeloid cells. Clinically continues to do well.

Sharat

Sharat Chandra, MD
Assistant Professor
Division of Bone Marrow Transplantation and Immune Deficiency
Cincinnati Children's Hospital Medical Center
Cincinnati, OH 45229

________________________________
From: CIS-PIDD [cis-pidd at lists.clinimmsoc.org]
Sent: Thursday, January 21, 2016 11:05 AM
To: CIS-PIDD
Cc: Abbott, Jordan
Subject: [cis-pidd] Cartilage Hair Hypoplasia Management

Hello All,

I am wondering what are everyone’s opinions regarding the timing of HSCT in Cartilage Hair Hypoplasia (CHH).  We have picked up a girl with CHH on the newborn screen recently, and she is approaching 3 months of age.  Would the risk outweigh the benefit if the transplant was done closer to age 1?  Would anyone not transplant at all?  Any other helpful advice would be appreciated.  Description of the patient is below.

Thanks in advance,
Jordan Abbott, M.D.
Assistant Professor of Pediatrics
National Jewish Health
1400 Jackson St., J333
Denver, CO 80206

80-day-old girl with T cell lymphopenia identified by newborn screen and rhizomelic limb shortening noted at birth.  She was subsequently found to have compound heterozygous RMRP mutations confirming the diagnosis of cartilage hair hypoplasia. Postnatal course was remarkable only for respiratory distress that resolved within a few days.  Baby has been feeding and growing with no infection.  No rash other than mild scalp seborrhea.  No maternal engraftment by VNTR. Labs are below:

Draw 3: 2 months old

Draw 2: 3 wks old

Draw 1: 2wks old

WBC count

3.9

4.9

Hemoglobin

14.2

14.6

Platelet count

305

238

Neutrophil count

1.6

2.2

Lymphocyte count

1.4

1.2

Monocyte count

0.7

1.3

Eosinophil count

0.2

0.2

ABSOLUTE CD3

216(18)

331(24)

290(24)

ABSOLUTE CD4

144(12)

238(17)

212(17)

ABSOLUTE CD8

26(2.2)

47(3)

38(3)

ABSOLUTE CD19

257(38.1)

411(30)

250(20)

ABSOLUTE CD16/56

472(39)

563(41)

637(52)

PHA Stim

25915 (same day ctrl 94467)

CD4CD45RA (%)

30

44.1

58

CD4CD31+ (%)

38.9

37.3

TCR/AB RESULT:

69.8

TCR/GD RESULT:

22.7

IgA

17

<10

IgM

80

40

IgG

462

788

TCR Vb1

4.35()

TCR Vb2

2.72(L)

TCR Vb3

1.64()

TCR Vb4

2.03()

TCR Vb5.1

7.06()

TCR Vb5.2

0.57(L)

TCR Vb5.3

0.45(L)

TCR Vb7.1

1.02(L)

TCR Vb7.2

0(L)

TCR Vb8

2.2(L)

TCR Vb9

0.83(L)

TCR Vb11

0.45(L)

TCR Vb12

2.61(H)

TCR Vb13.1

2.74()

TCR Vb13.2

1.04(L)

TCR Vb13.6

0.85(L)

TCR Vb14

4.11()

TCR Vb16

0.57()

TCR Vb17

3.12(L)

TCR Vb18

0.17(L)

TCR Vb20

1.02(L)

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