Hello all. Has any of you ever had a doctor suggest trying a bone marrow transplant or any other extreme therapy to treat the MGUS? To my husband and I, it seems extreme considering there's no proof the MGUS is what's inhibiting the immune system from working properly. It also seems to be a purely experimental idea, and we really don't want to be treated as lab rats any further (especially since there is so much documented success with monthly IVIG as a treatment). However, I'm curious to know if it's been suggested to anyone else, and also if it's ever been tried anywhere.

Hello Josephite, I suggest you read my recent comment in the topic on the MGUS. This laboratory abnormality is not a disease that must be treated. On the other hand it should be monitored because a possible evolution to myeloma. A bone marrow transplant is a very risky, very complicated and very expensive treatment which can be considered in some precise hematologic diseases that seriously threaten a patient. In the case of SCLS, the patient preparation for a transplant (induction) can lead to very serious or fatal leak. To my knowledge this treatment option has never been attempted in SCLS because it is too dangerous. An Indian patient with SCLS developed a multiple myeloma with frequent capillary leaks. He received a bone marrow transplant. He died a few months later because of the myeloma that has not responded to treatment however without new capillary leak. (Ghosh K, Systemic capillary leak syndrome preceding plasma cell leukemia, Acta Haematol. 2001; 106 (3): 118 - 21.) Claude Pfefferlé, Switzerland, cn.pfefferle@bluewin.ch

Thanks Claude. By Induction, do you mean Induction Chemotherapy? And if so, is that the only type of chemo that's dangerous to an SCLS patient? Or would all types of chemo be just as risky? I ask because the immunologist also suggested trying a certain chemo drug to wipe out the MGUS, but I can't remember the name of the drug. I do know there is a case that showed improvement after stem cell trasnplantation by bevacizumab, but I'm not 100% sure that's the drug she was referring to. She wanted to do more research on it to see if it had been tried anywhere before. The specialists did mention to us that MGUS is not normally something you treat, unless it has progressed to Myeloma. However, they believe the MGUS is inhibiting one or more proteins that are responsible for calming down the immune response. And so...their theory is it may be worth it to try treating the MGUS. However, my husband and I aren't yet interested in trying such high risk, experimental procedures. But I figure I should arm my brain with as much knowledge as possible so I don't sound like a complete idiot when I assault them with questions. :) For now, our plan is to stick with the monthly IVIG and see if that works.

Hello Josephite, Induction prior to bone marrow transplantation in hematological malignancies often includes total radiotherapy and chemotherapy. This treatment leads to death of blood cells and release of multiple factors (interleukin, interferon, cytokine, etc.) modulating the immune response. Some drugs used in a chemotherapy can clearly induce capillary leak (gemcitabine). If a leak occurs after an induction radio-chemotherapy, the risk of serious complications is enormous because the regulatory mechanisms are disrupted (loss of platelets, of white blood cells and interference of many immunological factors whose action are not always clear). Bevacizumab is a monoclonal antibody (IgG1) that binds VEGF (Vascular Endothelial Growth Factor) and prevents the proliferation of small vessels (capillaries). This drug is used in cancers of the bowel, breast, lung and kidney. New studies are made on lymphomas and other tumors, often in combination with other chemotherapy drugs The role of MGUS in the SCLS is not clear. It results from the production of an abnormal immunoglobulin by a clone of plasma cells. This protein does not induce a capillary leak. But it reflects a more complex immunological disorder not yet clearly understood. The idea to remove the paraprotein (MGUS) is good in itself. Indeed if we can get rid of the clone of plasma cells, one can hope to eliminate the immunological disorder. In my case, I tried chemotherapy with high-dose Thalidomid and I had two attacks of SCLS during treatment; one of these was a very serious leak. Then I tried the combination Thalidomid & corticosteroids as the classical chemotherapy against multiple myeloma. Unfortunately MGUS did not disappear and I had to stop the treatment because of severe side effects of Thalidomid (polyneuropathy) and corticosteroids (neuro-psychological disorders, diabetes, infections). Finally, the best _current_ treatment of SCLS is the monthly injection of polyclonal immunoglobulins (IVIG). Claude Pfefferlé

That is fascinating, thanks for your research Claude.

Yes - thanks. This is interesting information. Claude can you comment on Rituxin? My hematologist thinks this is a tremendous treatment and discusses it almost every time I see him. Another thought, I have been reading on the S1P1 drug types. Seems they have utility against the 'cytokine storms' that can lead to complication and death from the flu. These cytokine storms seem to be a leading cause of death among people who do not make through severe cases. Maybe I am grasping at straws, but I know that if I had not made it through my first episode, it would have been written that I died from complications that started with flu like symptoms, then dehydration that then led to capillary leakage, overzealous use of fluids, etc etc etc. My question is: How many flu deaths may be CLS related, and they never lived to get the diagnosis? Do you suppose the S1p1 class of drugs could be helpful?

Claude, I am extremely appreciative of you sharing that information with us. I am so sorry that you were so ill, and very glad you are stable now. Barney, Rituxin sounds familiar to me. I believe that may be the drug our immunologist was referring to.

Hello Josephite & Barney, Rituxin is marketed in Europe under the name Rituxan or Mab Thera. The scientific name is rituximab. This molecule is a monoclonal antibody directed against a particular protein (CD20) of the surface of certain white blood cells: B-lymphocytes. For some years it is regularly used against a white blood cell cancer : non-Hodgkin’s-B-cell-lymphomas (NHL). Recently the drug is tested against autoimmune diseases (thrombocytopenic purpura (auto-immune loss of patelets), hemolytic anemia (immune destruction of red blood cells), lupus erythematosus (autoimmune diseases agains many parts of the body), rheumatoid arthritis (inflammation of joints), transplant rejection with special humoral component (from B-lymphocytes) etc .... It is being studied against multiple sclerosis (inflammation of the brain) and chronic lymphocytic leukemia (cancer of lymphocytes) and other rare autoimmune diseases. To my knowledge there is no study on the prophylactic treatment of SCLS with rituximab. In case of a transformation of SCLS into lymphoma this treatment seems very promising. You should know that rituximab has frequent side effects that can be severe: leukoencephalopathy, massive destruction of normal and abnormal lymphocytes, lung diseases, serious heart and vascular problems, serious deterioration of white blood cells, bacterial and viral infections, gastro-intestinal complications, immune system disorders... etc. Claude Pfefferlé

Comment on S1P1 drug types : Fingolimod (Gilenya by Novartis Pharma) is an immunosuppressive molecule extracted from a Chinese mushroom in 1992. The mechanism of action was understood in 2002: fingolimod binds to sphingosine-1-phosphate receptors on the surface of lymphocytes, and after passing through the vessels into the brain, it binds to S1P1 receptors on the surface of nervous cells. Fingolimod also prevents the release of lymphocytes from the lymph nodes. It reduces the action of T-lymphocytes and therefore it has an inhibitory effect on the immune system. It is mainly used against multiple sclerosis (inflammation of the brain). This molecule is very promising and could have many uses in diseases involving cytokines (cytokines stroms). It also has side effects that could be serious : infections, eye disorders, heart rate disorder... Influenza can have a dramatic development with lung and multi-organ involvement. Its immunological disorders can lead to capillary leak similar to the SCLS. Currently we do not know what is the exact cause of “our” SCLS. A predisposing immunological cause could promote the action of a trigger factor ( viral, chemical, physical, other???). Claude Pfefferlé

Hello everyone, this week they offered my husband as well as Josefina, the option of doing chemotherapy with bortezomib + bone marrow autotransplant. There is a new entity that is the monoclonal gammopathy of clinical significance, which includes the patient with leak syndrome that presents a monoclonal component. The end of the treatment is as they commented to Josefina 6 years ago, to eliminate the clone producing the monoclonal component which (even without knowing its relation with scls) consider as responsible for the alteration in the immunity.
I would like to know if in these years someone has proposed the same thing.
Thank you

Hello all... I am very interested to see this post re-surface with new questions being asked. My haemotologist has lately mentioned the possible use of chemo. as a way to kill off the MGUS to then theoretically help eliminate the SCLS. Are there any further studies that indicate that this is a possible treatment form?

thanks from Canada,

Lisa

There is a review article "Narrative Review: The Systemic Capillary Leak Syndrome"  by Kirk M. Druey and Phillip R. Greipp,  Annals of Internal Medicine volume 153(2) 20 July 2010,   which describes several patients with SCLS and MGUS,    who received treatment for myeloma, leukemia  and POEMS syndrome.    Helen   

I am on mycophenolate motefil and corticosteroids as I reacted badly to IVIG in 2012. I also  now have auto immune liver disease, AI  kidney disease and an AI  form of vasculitis plus a few lessor AI disorders . Since I have been on these drugs, I have not had a capillary leak, except maybe a few minor ones.Prior I was a chronic 'leaker'.

This may be of interest or just a coincidence

However the side efects (mainly from the prednisone I think) have been  pretty devastating. Loss of bone, tissue fragility, bleeding  etc