Clinica Ruiz HSCT

I wanted to start posting very specific information regarding the Clinica Ruiz HSCT process outside of the daily blog so that all information could be found in one spot. Below you will find the process I went through.  I'm sure it varies slightly for others, but the result should be the same. 

I am making an attempt to organize this appropriately and make it easy for everyone to understand.  So far, I am grouping it into the following categories below.

  • My Timeline
    • This is just a short and sweet summary of MY timeline starting from the very first email request all the way through transplant.  Full details will be in the other sections as outlined.
  • Applying to Clinica Ruiz for HSCT
    • This shows my first attempts to contact Clinica Ruiz along with their email address and communications, document links and application image.
  • HSCT - The Mexican Way
    • Walk through the complete process including all drugs, the full calendar of events and what to expect from my perspective
  • Facilities and Staff
    • I wanted to give you an update on the apartments as well as the full staff you will be working with.  These people are amazing and the set up here is truly an advantage.  Of course, they're getting better with each group, but well on their way to being "the place to go".



My Timeline

For Yellow highlighted entries, more idetailed nformation can be found in the section below entitled -Applying to Clinica Ruiz for HSCT
For Blue highlighted entries, more detailed information can be found in the section below entitled -HSCT – The Mexican Way

Date HSCT Day Description
08/05/15 N/A I sent initial email for more information to Clinica Ruiz
08/16/15 N/A Received first response with application from from Clinica Ruiz (Danielle Smith)
11/27/15 N/A I emailed my actual completed application form back.
12/04/15 N/A Received confirmation that application was received and that I was being placed on the waiting list.
01/28/16 N/A Received email stating that I was being assigned for treatment on Mar 28, 2015 (WOW), along with instructions for everything needed 45 days in advance.
02/01/16 N/A I transferred the funds to Clinica Ruiz
02/02/16 N/A Received confirmation from Danielle that funds received
02/20/16 N/A I sent all update documents needed including bank transfer receipt, MRI reports, flight itinerary, proof of address, copies of passports
03/27/15 N/A My caregivers (Scott & Lauren) and I flew into Puebla, MX where we were picked up by one of the aides (Javier) and dropped off at our apartment.


Summary of Clinica Ruiz events shown below – full calendar posted separately with more details in HSCT - The Mexican Way section
03/28/15 Day -12 Welcome, Explanation of process and doubts, Paperwork, Lab tests, Spirometry test, CXR, Consultation with cardiologist, Consultation with Neurologist
03/29/15 Day -11 Medical History, Hematology consultation, Intravenous (chemotherapy) Cyclophosphamide, Apartment Medical kit delivery
03/30/15 Day -10 Intravenous (chemotherapy) Cyclophosphamide
03/31/15 through 04/04/15 Day -9 through  Day -5 Filgrastrim subcataneous medication (mobilizer) at apartment
04/05/15 Day -4 Filgrastrim subcataneous medication (mobilizer) at apartment, PIC line (catheter placement at hospital)
04/06/15 Day -3 Filgrastrim subcataneous medication (mobilizer) at apartment
04/07/15 Day -2 Apheresis (Cell Harvesting)
04/08/15 Day -2+ Apheresis (Cell Harvesting). I didn't get enough stem cells the day before, so required another round of apheresis. Intravenous (chemotherapy) Cyclophophamide and Mesna
04/09/15 Day -1 Intravenous (chemotherapy) Cyclophosphamide and Mesna
04/10/15 Day 0 Transfusion, stem cell placement. NEW BIRTHDAY ** I am here today **
04/11/15 Day +1 Blood samples every 48 hours (until granulocytes are recovered)

Hematology consultation every 48 hours (until granulocytes are recovered)
Filgrastrim every 24 hours upon doctor request

Application of Rituximab, MabThera (day to be established.
04/12/15 Day +2
04/13/15 Day +3
04/14/15 Day +4
04/15/15 Day +5
04/16/15 Day +6
04/17/15 Day +7
04/18/15 Day +8
04/19/15 Day +9
04/20/15 Day +10
04/21/15 Day +11
04/22/15 Day +12
04/23/15 Day +13 Medical Kit inventory – Fly Home

This image is not mine, but I think it does a great job of walking you through the timeline. Source: A. Arthur Fisher


Applying to Clinica Ruiz for HSCT

Clinica Ruiz email: hsct@clinicaruiz.com


I sent the following email to hsct@clinicaruiz.com on August 5, 2015:
I'm very interested in being considered for Homatopoietic stem cell therapy. In Dec. 2014 I began suffering from slurred speech, problems swallowing and feelings of vertigo. I was admitted to North Kansas City Hospital in North Kansas City Missouri USA. After many tests including MRI's, I was diagnosed with relapsing remitting multiple sclerosis. After my initial treatment of intravenous steroids to control the active areas of inflammation in my brain, I was put on Copaxone. My six month MRI again shows new active areas of inflammation and I was again put on intravenous steroids to control the inflammation. My neurologist has now prescribed Rebif which I will start soon.

I've read about the amazing possibilities of HSCT and look forward to any information you can give me on how to start the application process and cost. I'm looking forward to hearing from you -

Sincerely, Leslie Hansen
I received the following response from Danielle Smith on August 16, 2015:
Thank you for your e-mail, I have received all of your information. I would like to tell you more about our treatment.
You can find information about the HSCT performed in Clinica Ruiz in this link: http://www.clinicaruiz.com/hematologia/trasplants.htm
You can see the PDF file explaining the procedure by clicking on "HSCT for MS."
You can also watch a video of the treatment by clicking at the bottom on "Treatment Video "!
So far we have 2015 fully booked but I think new spaces will open for 2016 and 2017.
As soon as we have the openings (in a month or two) we will contact patients from the waiting list.
Please CONFIRM if you would like to be placed on this waiting list by filling out the APPLICATION form I include in this e-mail.

Best regards!
Danielle Smith



I did not send in my actual application form until 11/27/2015 as I was waiting to hear back from Chicago Northwestern on if I was going to be accepted into their trial.  (See HSCT page for more info there). Back in August I didn't know what my EDSS score was so needed to get this information as Clinica Ruiz would not accept the application without it. Below is a screen shot of the blank application form sent by Danielle.






HSCT - The Mexican Way

Agenda Group 1

In the above timeline, I posted only the summary of the events.  Below you will find the actual agenda for group 1 supplied by Clinica Ruiz.  There were two groups.  Group 1 had 8 people, and Group 2 had 6. 




Medication Scheme






 Medication Descriptions:
  • Cyclophosphamide -is a medication mainly used in chemotherapy. It is an alkylating agent of the nitrogen mustard type. 
  • Dexamethasone -is a type of steroid medication 
  • Ondansetron -  is a medication used to prevent nausea and vomiting caused by cancer chemotherapy
  • Pantaprazole - is used for short-term treatment of erosive esophagitis associated with gastroesophageal reflux disease.
  • Itraconazole: A triazole antifungal agent prescribed to patients with fungal infections. 
  • Trimetoprim/Sulfametoxazol: An antibiotic used mainly in the treatment of bladder infections. 
  • Acyclovir: An antiviral medication. 
  • Paracetemol: also known as acetaminophen or APAP, is a medication used to treat pain and fever.
  • Hydrocortisone: Cortisol is a steroid hormone, in the glucocorticoid class of hormones, and is produced in humans by the zona fasciculata of the adrenal cortex within the adrenal gland.
  • Ritixamub: RITUXAN is not chemotherapy. RITUXAN is a type of antibody therapy that can be used alone or with chemotherapy. They work in different ways to find and attack any remaining malfunctioning B cells that weren't destroyed during chemotherapy. 
  • MESNA: Mesna is used therapeutically to reduce the incidence of haemorrhagic cystitis and haematuria when a patient receives ifosfamide or cyclophosphamide for chemotherapy. These two agents, in vivo, may be converted to urotoxic metabolites, such as acrolein.  Mesna assists to detoxify these metabolites by reaction of its sulfhydryl group with α,β-unsaturated carbonyl containing compounds such as acrolein.[2] This reaction is known as a Michael addition. Mesna also increases urinary excretion of cysteine.


Clinica Ruiz Clinical Trial: NCT02674217

While I'm not part of the "trial", the below description is precisely the procedure that I am currently going through.  I wanted to make sure that interested parties know there is an official trial.

NCT02674217 Detailed Description:
Multiple sclerosis (MS) is a chronic, inflammatory, debilitating disease that causes destruction of central nervous system (CNS) myelin, with varying degrees of axonal damage. It mainly affects young adults and is twice as common in women as in men (1). Studies published from the 1990s brought animal models and theoretical considerations of hematopoietic stem cell transplantation (HSCT) being useful in the prevention and treatment of autoimmune diseases, with clinical responses in some patients, suggesting that high-dose chemotherapy followed by HSCT rescue could "reset" the immunological changes through the control of autoreactive clones, followed by immunological tolerance after immune reconstitution (2); this led to the conclusion that HSCT may be a viable therapeutic option for MS (1-6). Autologous HSCT have been done in patients with MS since 1996 and more than 700 HSCTs have been performed around the world (1-6). Most patients have been treated in small trials or in multicenter studies. In retrospective analyzes, a progression-free survival of more than five years after transplant has been observed, the neurological outcomes being considerably more favorable in patients with the relapsing-remitting type and/or those who showed an inflammatory pattern in magnetic resonance imaging (MRI) during the pre-transplant screening. Reports of good results, particularly in the aggressive forms of MS reinforce the effectiveness HSCT in MS patients with prominent inflammatory activity. The risk of transplant related mortality in HSCT for MS was conventionally considered very high but has declined since 2001 to 1.3% (2-6), this probably being the result of the changes in the conditioning regimens, thus reducing toxicity. Recent data, with more than 700 autologous transplants for MS in Europe, showed an overall survival of 92% in five years and a progression-free survival of 46%, the main cause of mortality and morbidity being the recurrence of the autoimmune disease (2-6). The consensus provides an indication of HSCT in patients with progressive MS unresponsive to conventional therapy and Expanded Disability Status Scale (EDSS) (1) between 3.0 and 6.0. The forms of the disease that might benefit from transplantation are: relapsing remitting, primary or secondary progressive, and the "malignant" form, provided there is evidence of inflammatory activity at the time of transplant indication.
Since 1993 our group has engaged in practicing HSCT using novel methods to both decrease the toxicity of the procedures and diminish costs (7-14); we have done over 400 HSCT for different diseases such as acute leukemia, chronic leukemia, aplastic anemia, myeloma, lymphoma, myelodysplasia and autoimmune diseases, including MS. Within the subset of autologous HSCT, the salient features of our method is that we conduct them on an outpatient basis (8-9, 15-16) and we avoid freezing and thawing the hematopoietic cells in order to both increase viability of hematopoietic cells in the graft and to reduce costs (8-9, 15-16) and we always employ peripheral blood stem cells (PBSC). All these changes have turned the practice of autografting in our hands in an affordable procedure which can be offered to individuals living in underprivileged circumstances such as those prevailing in developing countries (17). Having gained experience autografting hematological malignancies (8-9, 15) we aim to engage in a program of grafting non-cryopreserved autologous hematopoietic stem cells in patients with MS, employing a modification of the autografting conditioning regimen used in malignant diseases.
Material and methods
  1. Patients:
     
    Patients with MS refered to our center for a HSCT between November 2006 and July 2015 will be prospectively entered in the study. Individuals with a relapsing-remitting (RRMS) course, secondary progressive (SPMS), primary progressive (PPMS) or progressive relapsing (PRMS) will be included. Patients should have a Karnofsky performance status (18) above 70% and a EDSS score (1) of 6 or below. The study has been approved by the Ethics Committee of the Clinic Ruiz and all patients sign a consent form after being fully informed about procedure an possible complications.
  2. Peripheral blood stem cell mobilization and apheresis:
     
    The PBSC mobilization schedule will be done with cyclophosphamide (Cy) and filgrastim (G-CSF). Intravenous Cy (1.5 gr/m2) delivered in a 120 minutes period on days -13 and -12. Subcutaneous G-CSF (10 ug / Kg / bid) delivered on days -11 to -3. Using either a peripheral vein or a Mahurkar-type subclavian catheter, the apheresis procedures performed on day - 2 and - 1, using a Baxter C-3000 PLUS or an Amicus machine (Baxter Healthcare, Deerfield IL), and the Spin-Nebraska protocol (19). The apheresis objective is to reach at least 1 x106 viable CD34+ cells/Kg.
  3. Conditioning and autografting:
     
    As outpatients, intravenous Cy (50 mg(Kg) delivered along a 120 minute period on days - 2 and - 1 followed by MESNA (1000 mg/m2 along a 180-minute period), ondansetron 8 mg, dexamethasone 4 mg and pantoprazole 40 mg. After the intravenous Cy, ondansetron (4 mg every 12 h after chemotherapy), oral cotrimoxazol (800 / 160 mg every 24 h), oral fluconazole (200 mg) and oral acyclovir (400 mg every 12 h) will be used in all patients until granulocytes were greater than 0.5 x 109/L; in this period all patients will have laboratory workup and clinical studies every 48 h. After the recovery of the granulocytes, patients will be given rituximab (375 mg/m2 along a 3 h period), and in the following six months, cotrimoxazol 800/160 mg bid three times a week, acyclovir 800 mg daily. In addition, rituximab (100 mg) will delivered every two months along a 12-month period.
  4. Apheresis product preservation, studies and infusion:
The products of the apheresis and 1 ml aliquots were kept in ACD-A (Baxter Healthcare, Deerfield IL) at 4oC, in 300 ml transfer packs (Baxter Healthcare, Deerfield IL) composed of gas impermeable, polyvinyl chloride plastic film for up to 72 hours. Enumeration of the total white mononuclear cells (MNC) and CD34 positive cells is done by flow-cytometry (20) in an EPICS Elite ESP apparatus (Coulter Electronics, Hialeah, FL), using for the latter subpopulation the anti-CD34 monoclonal antibody HPCA-2 (Becton Dickinson, San José CA), gating in propidium iodide-excluding CD45(+) MNC population according to forward and 90° angle light scattering. Additional viability studies of the MNC uses propidium iodide exclusion and anti-cell antibodies on a flow cytometer. No purging procedures are performed. The apheresis products obtained on days - 2 and - 1 are reinfused to the patients on days 0 and +1 respectively after keeping them in the conventional blood bank refrigerator.

I'll update more later.. but wanted to go ahead and get this posted.

Hematopoietic stem cell transplant, HSCT, Multiple Sclerosis, MS, Myelin, Inflammation, Clinica Ruiz, Northwestern University, Chicago, Mexico, Israel, CTCI, Italy Careggi, Russia, Maximov, Avonex, Betaseron, Copaxone , Novantrone , Tysabri, Gilenya ,Tecfidera, DIAD, MRI, EDSS