[CIS-PAGID] Re : Re: Campath for Hemophagocytic syndrome
moshous despina
despina.moshous at nck.aphp.fr
Sat Dec 3 06:14:20 EST 2011
Dear colleagues,
We usually do a first course of a total of 2,5mg/kg Campath H1 over three days, that is 0,5 mg/kg day 1, followed by 1mg/kg on day 2 and 3. The reason for this is, that patients with activation syndrome may have a extremely bad tolerance of the first (and maybe second) Campath, so we go very slowly for the first Campath, planning an infusion over 8 to 12 h (or even more depending on tolerance), starting with a very low dose/hour and increasing the dose/hour only very slowly if tolerance is ok. the Campath needs to be co-medicated with Methylprednisolone as well, we give 0,3 mg/kg at H0, H+4 and H+8 (the H+8 may not be given on day 2 or 3 if tolerance is ok) We do also premedication with antihistaminics at H-1.
In these patients, we use concommitantly methylprednisolone 2 mg/kg/day in two doses and go for ciclosporine ivc after the campath.
Sometimes you need to repeat Campath or to switch to ATG, if the response is not sufficient. Overall we have good results with the Campath approach (when used as first line treatment) and needed to switch to ATG only in a minority of patients. We thouroughly check for virus (EBV, CMV, HHV6...) that may trigger the activation but I guess you looked for all of this.
If there is clear evidence for cerebral involvement (lymphocytes at LP or abnormal MRI signals) we do intrathecal injections of steroids and MTX.
Indeed this is the approach for activation syndrome we use in patients with proven or suspected genetic forms of lymphohistiocytosis, in (adult) patients with suspicion of underlying malignany this approach may mask the evolution, as you may even obtain a remission in lymphoma in the beginning. We once observed this, the lymphoma of the T cell lineage in a 3 year old girl being diagnosed only at relapse... Not having all the details of your patient, I cannot affirm that our approach is the best treatment option for your patient right now, but if you consider him to be a form of lymphohistiocytosis, I guess we would try the Campath, also in an adult patient.
Feel free to contact me for further information.
Best regards and good luck with your patient
Despina MOSHOUS MD PhD
Unité d'Immunologie et d'Hématologie Pédiatriques
Hôpital Necker-Enfants Malades
149, rue de Sèvres
75015 Paris
France
Tél +33 1 44 49 48 23
Fax +33 1 42 73 28 96
et
Dynamique du Génome et Système Immunitaire
(Genome Dynamics in the Immune System)
INSERM U768 Pavillon Kirmisson
Hôpital Necker Enfants Malades
149 rue de Sèvres
75015 Paris, France
----- Message d'origine -----
De: stephan.ehl at uniklinik-freiburg.de
Date: Vendredi, Décembre 2, 2011 9:43 pm
Objet: Re: [CIS-PAGID] Campath for Hemophagocytic syndrome
À: pagid at list.clinimmsoc.org
Cc: despina.moshous at nck.aphp.fr
> Don,
>
> Despina Moshous (cc) will be able to provide you with details of the
> Paris protocol.
> There is also significant experience with
> Campath in Cincinnatti - call Michael Jordan or Lisa Filipovic.
>
>
>
> Beste Grüße
>
> Prof. Dr. Stephan Ehl
> Wissenschaftlicher Direktor
>
> UNIVERSITÄTSKLINIKUM FREIBURG
> CCI - Centre of Chronic Immunodeficiency
>
> Breisacher Str. 117 - 2. OG, 79106 Freiburg i. Brsg., Germany
> phone: +49(0)761.270-77300
> Sekretariat +49(0)761.270-77550 fax +49(0)761.270-77600
> e-mail: stephan.ehl at uniklinik-freiburg.de
>
> -----pagid-bounces at list.clinimmsoc.org schrieb: -----An:
> "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>
> Von: "Donald Cuong Vinh, Dr"
> Gesendet von: pagid-bounces at list.clinimmsoc.org
> Datum: 02.12.2011 07:17PM
> Betreff: Re: [CIS-PAGID] Campath for Hemophagocytic syndrome
>
> 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
>
>
>
> Le message que vous avez reçu, ainsi que toute pièce jointe, a été
> envoyé à l’intention exclusive de son ou de ses destinataires; il est
> de nature confidentielle et peut constituer une information
> privilégiée. Si vous n’êtes pas le destinataire prévu, soyez avisé que
> toute autre utilisation non autorisé, dénonciation, copie,
> distribution ou la prise d’une action sur la foi du contenu de ce
> message et de toute pièce jointe est strictement interdite. Si vous
> n’êtes pas le destinataire prévu, veuillez en aviser immédiatement
> l’expéditeur par retour de courriel et supprimer le message et toute
> pièce jointe de votre système.
>
> 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.
> ________________________________
> 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
>
>
>
> Le message que vous avez reçu, ainsi que toute pièce jointe, a été
> envoyé à l’intention exclusive de son ou de ses destinataires; il est
> de nature confidentielle et peut constituer une information
> privilégiée. Si vous n’êtes pas le destinataire prévu, soyez avisé que
> toute autre utilisation non autorisé, dénonciation, copie,
> distribution ou la prise d’une action sur la foi du contenu de ce
> message et de toute pièce jointe est strictement interdite. Si vous
> n’êtes pas le destinataire prévu, veuillez en aviser immédiatement
> l’expéditeur par retour de courriel et supprimer le message et toute
> pièce jointe de votre système.
>
> 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.
> ________________________________
> 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>
>
>
More information about the PAGID
mailing list