[CIS-PAGID] Campath for Hemophagocytic syndrome

[Donald Cuong Vinh, Dr]

Thank you for your prompt replies.
He's actually quite ill, Ashish. Fever, dropping platelet counts, ferritin increasing (31 000 ----> ~350 ---> 3200) with headaches. This occurred while on lowering doses of Dexamethasone (off VP16 & Cyclosporine for about 10 days). These have been re-initiated, with modest improvement.

Any idea on the alemtuzumab regimen/dosage? Dr. Verbsky, do you or Dr. Talano know of the dosage that has been used, even if not published?

Thanks
Don



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From: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org] on behalf of Ashish Kumar [Ashish.Kumar at cchmc.org]
Sent: Friday, December 02, 2011 11:09 AM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] Campath for Hemophagocytic syndrome

If your patient is not acutely ill, I would reinduce with Dexamethasone alone first and then add Etoposide if needed. If refractory to both of these, then try Campath. You will need to leave him on low dose or pulse dose Dexamethasone until transplant, keeping an eye on viruses.


Ashish Kumar, MD, PhD
Assistant Professor
Cincinnati Children's Hospital Medical Center
Cincinnati, OH


>>> "Donald Cuong Vinh, Dr" <donald.vinh at mcgill.ca> 12/2/2011 10:05 AM >>>

Dear Colleagues,

We have an early 30s year old man who is re-presenting with hemophagocytic syndrome. His first presentation was approximately 3 months ago, with the full constellation (although no evidence of hemophagocytosis on bone marrow). He was treated as per HLH protocol (VP-16, Cyclosporine, dexamethasone) with very good improvement. However, the syndrome has recurred. Extensive infectious & rheumatologic w/u is negative; the possibility of malignancy remains, although to date, there has been no proof of this. Cells stored away for genetic evaluation (esp. in light of the paper on hypomorphic mutations by Dr. Filipovich's group). Transplant work-up in progress.

>From a management perspective, would you proceed to alemtuzumab? At CIS in Chicago in May, there was an oral presentation on this, and as far as I can remember, the results were encouraging (although I don't remember the etiologies of the HLH). If so, what dosage? If not, re-induction with the above?

Thanks
Don


Donald C. Vinh, MD
Assistant Professor
Division of Infectious Diseases,
Division of Allergy & Clinical Immunology
Dept of Medicine; Dept of Medical Microbiology; Dept of Human Genetics
McGill University Health Centre - Montreal General Hospital
1650 Cedar Ave, Rm A5-156
Montreal, Quebec,  Canada H3G 1A4
Ph: 514-934-1934 x42419 (office); x42811 (admin assist)
Fax: 514-934-8423
e-mail: donald.vinh at mcgill.ca



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This communication and any attachment are directed in confidence solely to the person(s) listed above; the materials in this communication are private and may constitute privileged information. If you are not the intended recipient, be advised that any unauthorized use, disclosure, copying, distribution or the taking of any action in reliance on the contents of this information and any attachment is strictly prohibited. If you have received this email in error, please immediately notify the sender by return e-mail and delete this communication and any attachment immediately from your system.
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From: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org] on behalf of Dr. Carsten Speckmann [carsten.speckmann at uniklinik-freiburg.de]
Sent: Friday, December 02, 2011 9:45 AM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] Partial CD4 deficiency, autoimmunity, bronchiectasis

As pointed out by you there is for sure a T cell problem. What is the picture of the muscular hypotonia? Enamel defect?
Ca chanelopathies present with normal absolute lymphocytes, clinical T cell deficiency and sometimes (i.e. STIM1) with autoimmunity.

Carsten

Am 02.12.11 15:07, schrieb Eleonora Gambineri:
Dear all I would like your inputs on the case below:
21 mo/old girl
FAMILY HISTORY unremarkable
MEDICAL HISTORY: hx at birth unremarkable. At 7 mo of age she started to suffer of recurrent respiratory infections (mainly pneumonitis and bronchitis); at 15 mo: ? Enterovirus encephalitis (no evidence at brain MRI and EEG, but positive PCR in liquor); afterwards she had 4 pneumonitis (June-Sept 2011) with slow recovery
LAB W/U
Normal LFTs/U&E
Immunological W/U:
WBC 9900/ul L 27.6% (2732/ul), Eo 22.6% (2237/ul) N 40.4% B 1.7%, M 3,8%; Hb 11 g/dl, ferritin 2,7 ng/ml
Partial CD4 deficiency (400-500/ul) with low/absent CD4/CD45/CD31+ cells (absent TRECs) and expansion of memory phenotype both in CD4 and CD8 subsets. Normal B cell numbers with good percentage of memory B cells.
Antibody responses: POSITIVE to measles and varicella, NEG to tetanus, HBV, difteria, HSV IgG positive, EBV IgG/IgM negative, HHV6 IgG/IgM negative
IgG 900 mg/dl, IgA64 mg/dl, IgM 233 mg/dl (increased), IgE negative
TCR repertoire: high Vb6-5, 6-6, 6-9 (on CD8)…not sure if done on CD4
In vitro lymphocyte proliferation assay: low response to PHA and aCD3/CD28+IL2 (However, it was not confirmed in another lab)
Alpha feto-protein: slightly deranged (13 UI/ml, NV 0.1-4.9)
Coombs POSITIVE IgG; ANA POSITIVE (1:1280); aTPO POSITIVE (normal thyroid function)
Infection W/U
CMV PCR POSITIVE on BAL; Pseudomonas Positive on BAL
CMV, Adeno, EBV PCR negative on blood
IMMAGING:
Chest CT: bronchiectasis; Thyroid US: normal, lateral-cervical LN with increased size; Abdomen US: nil; Heart US: nil; Thymus should be present, but ask to review the scan (results still pending)
O&E
Normal growth
No signs of intestinal malabsorption
Ligamentous Hyperlaxity
Muscle hypotonia (normal EMG at lower body, partly altered at upper body, anti AchR Ab ongoing)
No dimorphisms (she was reviewed by Geneticist); No hair alterations; No bone abnormalities (at femur X Ray, total skeleton X-Ray TBD)
No rash, but diffuse itchiness
Chest: when in good conditions, crackles all over the chest with minor distress. SatO2 in AA 93%, with episodes of desaturation at night. She is at the moment on FKT.
Liver: 1-2 cm below costal margin
CV: systolic hypertension of unknown origin (no renal impairment, no steroid treatment)
DIFFERENTIAL
At the moment the following condition have been excluded:
- HLA I and II deficiency
- ADA/PNP deficiency
- RAG1/RAG2 mutations
- IL7Ra deficiency
- DGS (CGH array negative)
- AT (aFP 13 is it indicative? no clinical signs?)
- CHH, sequencing of RMRP ongoing at the moment
Any other suggestion?
We are assessing the patient to evaluate a possible HSCT from her matched-sibling brother, although given the unknown nature of her immune defects and the compromised pulmonary conditions do you think it is feasible to proceed? My worry is regarding the thymus. What if there is an unknown thymus defect (immune deficiency and dysregulation)? This might question the immune reconstitution after HSCT. On the other hand the infection history of this girl as well as her immune function do not suggest a mild disease course and BMT seems the only option. I know it is a tricky question, but I will really appreciate your help.
Thanks for your cooperation!
Best wishes,
Eleonora
*******************************************************************
Dott.ssa Eleonora Gambineri
Ricercatore Universitario

Universita' degli Studi di Firenze, Dipartimento di Scienze per la Salute della Donna e del Bambino
Ospedale Pediatrico "Anna Meyer", Dipartimento di Oncoematologia-Unità TMO
Viale Gaetano Pieraccini, 24
50139 FIRENZE
Tel 055 5662405 (ufficio)
       055 5662606 (reparto T.M.O.)
Fax 055 4221012
e-mail: eleonora.gambineri at unifi.it<mailto:eleonora.gambineri at unifi.it>; e.gambineri at meyer.it<mailto:e.gambineri at meyer.it>

Eleonora Gambineri, MD
Researcher/Assistant Professor

University of Florence, Department of Sciences for Woman and Child's Health
"Anna Meyer" Children's Hospital, Department of Haem/Onc-BMT Unit
Viale Gaetano Pieraccini, 24
50139 FIRENZE
ITALY
Tel +39 055 5662405 (office)
       +39 055 5662606 (BMT Unit)
Fax +39 055 4221012
e-mail: eleonora.gambineri at unifi.it<mailto:eleonora.gambineri at unifi.it>; e.gambineri at meyer.it<mailto:e.gambineri at meyer.it>
********************************************************************




--
Dr. med. Carsten Speckmann
Facharzt
Zentrum fuer Kinderheilkunde und Jugendmedizin
Centrum fuer Chronische Immundefizienz - CCI
Universitaet Freiburg
Mathildenstr. 1
79106 Freiburg
Germany

phone: +49 (0)761-270 43010
mail: carsten.speckmann at uniklinik-freiburg.de<mailto:carsten.speckmann at uniklinik-freiburg.de>
web: www.cci.uniklinik-freiburg.de<http://www.cci.uniklinik-freiburg.de>