Transplantation of hematopoietic stem cells in pediatric oncology

1. Transplantation of hematopoietic stem cells in pediatric oncology Vladivostok State Medical University Foreign languages department Scientific advisor: Korotkova E.A. Performed by: Batmanova N.A. Vladivostok 2012

2. The aim: to summarize the indications for hematopoietic stem cells transplantation in children, to identify the main complications, and to demonstrate the results of the HSCT for various kinds of nosology, based on the results of specialized bone marrow transplantation unit.

3. Transplantation of hematopoietic stem cells – the introduction of the recipient suspension of hematopoietic stem cells (HSC) after the appointment of myeloablative radiation doses or maximally tolerated doses of cytotoxic agents; • Stem cells– a population of undifferentiated cells with the capacity to divide for indefinite periods, to self-renew and to generate a functional properties and functions. The basic contents: Pic.1 Normal bone marrow cytology

4. The sources of stem cells: • Bone marrow - Traditional source of precursor cells; - Requires intake in the operating room; - Used mostly in allotransplantation. • Peripheral blood - requires the mobilization of donor precursor cells with the aid of chemotherapy, hematopoietic growth factors, or both; - used primarily in autotransplantation. • Cord blood - taken from the umbilical cord after birth.

5. The main types of hematopoietic stem cell transplantation; • Autologicaltransplantation As a source of cells the patients own precursor cells are used; • Syngeneic transplantation Possible when a potential recipient has an identical twin, who can become a stem cell of a precursors donor; • Allogeneic transplantation When other donor is used for transplantation, who differ in histocompatibility.

6. The basic indications for allo-HSC transplantation: • Acute lymphoblastic leukemia in second remission, in first remission in case of relapse; • Сhronicmyeloid leukemia; • Severe forms of BM insufficiency; • Some hereditary blood diseases; • Some non-hematological hereditary diseases; • Immunodeficiency conditions. The basic indications for allo-HSC transplantation: • Acute lymphoblastic leukemia in second remission, in first remission in case of relapse; • Solid tumors (neuroblastoma, brain tumors, osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma, other tumors. Absolute indications for allo-HSC are identical and considered individually applied for each patient!

7. Post-transplantation complications Pict.2 Macular rush as an expression of GVHR 1. Acute reaction «graft-versus-host» (GVHR) – clinicopathologic syndrome, including skin lesions, liver and intestine.

8. Post-transplantation complications Pic. 3 Macular rush on the soles as an expression of acute GVHR • Characterized by spotted red rush with itching and soreness; • Should be differentiated with chemotherapy induced rush, drug allergy and viral exanthema.

9. Post-transplantation complications 2. Chronic reaction «graft-versus-host» Clinical-pathological syndrome that involves the skin, liver, eyes, oral cavity, gastrointestinal tract, lung and neuromuscular systems. Pic. 4. Skin lesions in chronic GVHR

10. Post-transplantation complications Pic. 5 Aseptical skin lesions in chronic GVHD

11. The event-free survival of patients with Ewing's sarcoma family of tumors n=50, after 2000 year, 64%, 74 months. n=24, before 2000 year, 8%, 24 monthes. Overall, among 104 patients at high risk groupevent-freesurvivalwere 64% at median follow-up 74months.

12. Event-free survival of patients with neuroblastoma of high risk group 17 patients of high risk group; 15 patients – stage IV of neuroblastoma; Event-free survival 35% at median follow-up 37 months

13. 1,0 ,9 ,8 ,7 ,6 ,5 ,4 ,3 Survival ,2 ,1 0,0 0 20 40 60 80 Months after treatment Event-free survival of patients with relapses of nephroblastoma 29,4% Medium follow-up 40 months 10 out of 34 patients (29,4%) are alive without evidence of the disease

14. Haploidentical bone marrow transplantation • 20 patients 15 girls 5 boys • Average age - 11 years 14 patients- 6 patients– solid haemoblastosis tumors • 21 haploidentical transplantation (1 patient was transplanted twice)

15. Overall survival after haploidentical transplantation

16. Conclusions: • Transplantation of hematopoietic stem cells is one of the most effective methods of treatment of various diseases of the blood system in children; • HSCT allowed to increase disease-free and event-free survival in patients with Ewing′s sarcoma, neuroblastoma, relapses of nephroblastoma and patients with hemoblastosis; • Infectious complications and acute graft-versus-host were the main complication and cause of death in patients after allogeneic HSCT. Correction of these conditions will improve remote results and life quality of patients after allogeneic HSCT; • The efficiency of method depends not only the relapse, but also on the stage of disease at the moment of transplantation.

17. Thank you for attention!