Assoc. Dr. Ilina Micheva, M.D.: Transplantation of stem cells gives a chance to cure leukemia

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Assoc. Dr. Ilina Micheva, M.D.: Transplantation of stem cells gives a chance to cure leukemia
Assoc. Dr. Ilina Micheva, M.D.: Transplantation of stem cells gives a chance to cure leukemia

Assoc. Dr. Ilina Micheva, MD, is the head of the Department of Transplantation at the Hematology Clinic at the "St. Marina" - Varna. He graduated in medicine in Varna in 1993. In 1998 he acquired a speci alty in internal medicine, and in 2006 in clinical hematology. From 1999 to 2000, he worked as an associate and postgraduate student at the Hematology Clinic of the Medical University of Patras, Greece, where he participated in various projects. In 2005, he defended his thesis on "The role of dendritic cells in hematopoietic disorders in patients with myelodysplastic syndrome". Since 2006, he has been working at the Hematology Clinic of the Varna Hospital as a chief assistant.

Doc. Micheva's main scientific interests are in the field of myelodysplastic syndromes, acute leukemia, stem cells. There are publications in several foreign and domestic journals and a number of participations in international scientific forums in various areas of hematology. He is a member of the Bulgarian Hematology Society, the European Hematology Association, the Greek Flow Cytometry Association. In October 2018, Assoc. Prof. Micheva was awarded an award in the "Innovations" section for the establishment of the transplantation department.

Prof. Micheva, since when have you been implementing stem cell transplantation in the hospital?

- In Bulgaria, there are currently two centers for the transplantation of allogeneic stem cells - the center in Sofia, which has been operating for more than 15 years, and for several years the center in Varna, where all patients in need of transplants are such treatment, from a region covering 1/3 of the territory of Bulgaria. The only transplant department in Eastern Bulgaria opened its doors at the end of UMBAL "St. Marina" - Varna, thus the hospital starts a new activity - performing autologous and allogeneic hematopoietic stem cell transplants in adults and children. The first autologous transplant was performed in June 2015 and the first allogeneic transplant in August 2017, with our youngest patient being 6 years old and our oldest being 67 years old.

From June 2015 to September 2018 in the transplant department at UMBAL "St. Marina" - Varna, 71 autologous and allogeneic hematopoietic stem cell transplants were performed in adults and children. If these patients had sought help in foreign clinics, it would have cost the state more than BGN 15 million, and their treatment in Varna would have cost about BGN 3 million. With this activity, the Varna University Hospital has saved the state over BGN 12 million.

What is the difference between autologous and allogeneic transplants?

- In autologous transplants, the patient himself is the source of the stem cells that, after high-dose chemotherapy, are transfused to help the body recover from this rather toxic therapy, which is done to eradicate the disease as much as possible deeper. It is mainly used in patients with myeloma, large cell lymphoma, Hodgkin's disease.

Allogeneic transplants use cells from relatives, mainly siblings. Recently, another type of transplantation has become quite popular, in which other relatives - parents and even children - can also become donors. There is a patient who is being discussed for a transplant with her daughter's donor.

What is autologous transplantation itself?

- Autologous transplantation is a high-dose therapy in which the patient's previously collected stem cells are transfused, thus helping the body recover faster.

What is the therapeutic power of stem cells called by this lyrical name - hematopoietic. Is this a special kind of stem cell?

- No, they are not a special species. It is these stem cells that have the potential, when placed in an appropriate environment, such as the bone marrow, to target and reside there, begin to proliferate, and give rise to the major cell lineages that ultimately lead to the formation of mature leukocytes, platelets and erythrocytes.

These are cells that are normally found in the peripheral blood of all he althy people.

You have been treating patients with this method for a long time. What is the balance sheet regarding its effectiveness? After applying it, can the patient be said to be cured?

- If we talk about autologous transplantation, this method does not lead to a complete cure. But in many of our diagnoses, it's a way to maximize the remission period, and for many of the lymphomas and lymphoma patients, that's hugely important. This is the period in which they have a normal quality of life.

And with allogeneic therapy, can the patient be cured?

- Allogeneic transplantation is the only method in hematological practice that leads to the possibility of a complete cure, to eradication of the disease.

In allogeneic transplantation, the source of stem cells is a foreign donor. It must be a he althy person who can be a relative or an unrelated donor, with leukocyte typing beforehand to determine the most suitable formula (thus choosing the most suitable of all donors). In the absence of a related donor, we have to look for donors in international donor banks. So far, we have had quite a few such transplants, with donors being people from other countries.

We have a National Public Donor Bank. Are there not enough donors in it?

- Unfortunately, in Bulgaria the number of those willing to become donors is very small. Perhaps due to the not particularly popular of hematological diseases and the stem cell transplant procedure.

A campaign was launched with the Student Council of the Medical University in Varna to expand the register. So far, mostly students are responding to the appeal. And for this reason, this should become a priority task of every hematology community in Bulgaria, in order to motivate people to donate their stem cells.


Assoc. Dr. Ilina Micheva

What should those who wish to become stem cell donors do?

- For this purpose, only the donor is required to give a blood sample, which is sent to Bulgaria's only laboratory in Alexandrovska Hospital, which performs leukocyte typing to search for compatibility.

All who have sent their blood sign an informed consent that they want to become a donor. If necessary and when compatibility is found between them and the respective patient, they are already searched for and only then the stem cell donation procedure begins. I.e. in the beginning they are only potential donors. They may never have to donate stem cells, but they are in the data bank. And if it happens that their formula matches that of a patient in need, then they are sought out and must give their final consent to start the whole cell harvesting procedure.

Can these donor cells be extracted only in certain places in Bulgaria?

- In all centers where transplants are done, there are also laboratories where stem cells are extracted. This is a special procedure that is performed by highly qualified personnel trained for this.

Once these stem cells are taken from the donor, is the donor's body damaged in any way?

- No way! Collected stem cells regenerate very quickly - bone marrow has this potential.

How does the stem cell transplant itself proceed already in the sick person who needs this therapy?

- Patients receive chemotherapy that is specific. It aims to free the bone marrow, on the one hand, and destroy all remaining tumor cells, as well as to suppress the immune system so that it can accept the foreign cells. So this is the first step.

The second step is the transfusion of the stem cells themselves, which is very similar to a blood transfusion. After that, the most difficult part begins - the restoration of normal blood production. We expect the cells that we have transplanted to get into the bone marrow and start making new blood cells, already donated. This is a critical period in which the body needs very serious supportive therapy. Throughout this period, the patient also receives immunosuppressive therapy to suppress possible mechanisms of rejection of the donor cells.

After that, all patients who have undergone this procedure are subject to very strict, at first weekly, then monthly control throughout their life. It should be monitored for the manifestation of various complications - first in the early, then in the late phase of transplantation. They remain fragile patients, under constant supervision by specialists and special care.

From your observations during these years of applying the method of stem cell transplantation, in which diseases do you achieve the best results or is it individual?

- It is absolutely individual. It depends on the diagnosis, on what response to the therapy the transplant started with. Because there are transplants that are done in absolutely resistant patients who have not responded to chemotherapy. That's why this transplant is lifesaving for them.

When done in patients with a very good response from previous chemotherapy, then the results are significantly better. And such patients are with acute leukemia, with acute myeloid or with acute lymphoblastic leukemia, in which this is the only method of treatment. Patients with non-Hodgkin's lymphomas, with Hodgkin's disease, can be well affected. But of course it is individual. It depends on so many factors.

What distinguishes acute leukemias from other oncological diseases in terms of their development and course?

- Their main difference is that acute leukemias are one of the most malignant hematological diseases. These are diseases of the blood and account for 6 to 8% of newly diagnosed cancers annually.

The disease progresses quite quickly, during which a violation of normal blood production is observed - it stops the maturation of cells in the bone marrow and young, immature and non-functional cells appear in the blood.

Symptoms in acute leukemias are associated with a decrease in erythrocytes and platelets, which leads to easy fatigue, lethargy, the appearance of blue spots, bleeding from the mucous membranes, an increase in temperature, the appearance of infections that are difficult to treat with antibiotics. A blood count reveals the presence of anemia, a low platelet count, and usually, but not necessarily, an elevated total white blood cell count. If any of these symptoms appear, a consultation should be carried out immediately, since the timely initiation of treatment in acute leukemia is extremely important for the outcome of the therapy.

Your last patient is a 17 year old boy. What treatment did you give him and what is his current condition?

- We performed an allogeneic bone marrow transplant in this patient. The boy has a very rare and difficult to treat form of leukemia. In December 2016, he was diagnosed in our Clinic of Pediatric Clinical Hematology and Oncology. He was given chemotherapy which resulted in remission within the first month of treatment and the child has been in very good condition for 16 months. However, at the end of this period, a relapse was registered, for which the only alternative for treatment is an allogeneic transplant. The transplant was successful, with fully matched hematopoietic stem cells harvested from his sibling. The child is recovering in the Children's Hematology and Oncology Clinic. Fortunately, he is now in very good condition, in complete remission, with all indications that the donor cells are developing well. The disease has been suppressed, but it is still too early to give longer-term predictions. The patient has already passed the 100th day, which is critical for all transplants. He is constantly with us for monitoring and control of his condition.

If a patient does not respond well enough or rejects his transplanted stem cells, can a second, third such transplant be undertaken?

- It is possible, yes. There is such an option for repeated routine transplantation, as well as the possibility of other forms of treatment after transplantation, through the use of donor leukocytes. I.e. there are different methods that can be used to respond after a failed first allogeneic transplant. We never give up - this is the first criterion for success. We fight for every patient until the last!


Anyone can become a donor

“Anyone can become a donor. It is preferable that these are young people, completely he althy. Of course, the stem cell collection procedure is completely safe. Some mild side effects are possible during the period of stimulation of the body to allow these stem cells to come out into the periphery for their final collection. Even then there is no need to monitor the donor. Only one control blood test is done within the next month. The stem cell separation procedure takes place with 4-5 days of growth factor stimulation, which is administered in the form of subcutaneous injections. There may be slight redness and pain at the injection site, as well as bone pain, but these are symptoms that quickly subside afterwards

After separation, the stem cells are processed and stored at a temperature of -180 degrees, in liquid nitrogen, indefinitely

Transplantation can be used for almost all hematological diseases. There are enough indications for transplantation even in children", added the expert

Is the treatment covered by the He alth Insurance Fund?

“The he alth fund pays a single amount for the procedures related to the transplant itself. What is a serious problem at the moment, in my opinion and in the opinion of most of my colleagues who are involved in this, is the underfunding of the follow-up treatment, meeting all the costs of research, follow-up, monitoring and treatment, when necessary, of the complications. Because according to all statistics, it turned out to be the most expensive part of treating patients, especially within the first year.

There is also a certain amount set aside, but it is only for some of the complications and does not cover a large part of the costs that have to be incurred for such patients , explained Prof. Micheva.