Year : 1996 | Volume
: 7 | Issue : 2 | Page : 199--202
The Experience of Bone Marrow Transplantation at Riyadh Armed Forces Hospital
Maadh Al Douri1, Magda Wahdan1, Akram Al Hilali1, M Talal Jeha1, Ferdinand Zwaan1, Peter Van Dijken2, Fatima Batniji2, Mohiuddin Qasim3, Khalid Al Anazi1, Fawzia Al Saghair1, Tariq Shafi2,
1 Department of Pathology, Riyadh Armed Forces Hospital, Riyadh, Saudi Arabia
2 Department of Pediatrics, Riyadh Armed Forces Hospital, Riyadh, Saudi Arabia
3 Department of Oncology, Riyadh Armed Forces Hospital, Riyadh, Saudi Arabia
Maadh Al Douri
Consultant Hematologist, Department of Pathology, Riyadh Armed Forces Hospital, P.O. Box 7897, Riyadh 11159
This is a report about the program of bone marrow transplantation (BMT), which was established in 1989 at the Armed Forces Hospital in Riyadh, Saudi Arabia. We follow the strict international protocol of pre transplant assessment of the donor and the recipient, BMT conditioning by Cyclosphosphamide and Basulphan or body irradiation, BM harvest and processing, graft versus host disease prophylaxis by cyclosporin and methotrexate, and post-transplant care. Since the start of the BMT programme at the Armed Forces Hospitals in Riyadh in May 1989 and until the end of March 1996, fifty nine allogeneic and one autologous transplants have been performed. Chronic myelocytic and acute myeloid leukemia were the principal indications for BMT in our institute. The acturial five years survival of BMT in these two conditions was 67% and 47% respectively. Besides allografting, we finished the preparations for autologus BMT and peripheral blood stem cells transplantation, which may be used for treating patients with solid tumors and leukemias who are not suitable for allogenic transplantation due to older age or donor unavailability.
|How to cite this article:|
Al Douri M, Wahdan M, Al Hilali A, Jeha M T, Zwaan F, Dijken PV, Batniji F, Qasim M, Al Anazi K, Al Saghair F, Shafi T. The Experience of Bone Marrow Transplantation at Riyadh Armed Forces Hospital.Saudi J Kidney Dis Transpl 1996;7:199-202
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Al Douri M, Wahdan M, Al Hilali A, Jeha M T, Zwaan F, Dijken PV, Batniji F, Qasim M, Al Anazi K, Al Saghair F, Shafi T. The Experience of Bone Marrow Transplantation at Riyadh Armed Forces Hospital. Saudi J Kidney Dis Transpl [serial online] 1996 [cited 2020 Apr 7 ];7:199-202
Available from: http://www.sjkdt.org/text.asp?1996/7/2/199/39528
Since the end of the 1960's bone marrow transplantation (BMT) has increasingly become a standard procedure for treating a variety of disorders including hematological malignancies, bone marrow failure, hemoglobinopathies, immune deficiency states, solid tumours etc. The success of the procedure has increased as a result of improving the supportive care, as well s better understanding of the immunological changes accompanying the transplantation, and finding new sources of stem cells for transplantation. The basis of the BMT Procedure is exposing the patient to myeloablative conditioning therapy in the form of chemotherapy with or with out radiotherapy, following which the patient is rescued by transfusing HLA-identical bone marrow or peripheral blood stem cells (PBSC) from a fully compatible sibling or unrelated donor, or autologous marrow or PBSC harvested from the patient himself prior to the conditioning therapy. Following this procedure the patient passes through a period of pancytopaenia lasting in average 3-4 weeks during which the patient needs to be nursed in specialised units where he/she would be supported by special nutrition, blood component therapy, intensive antimicrobial therapy, and immunosuppressive therapy to prevent rejecting the new bone marrow or the occurrence of graft versus host disease.
Subjects and Methods
BMT at Riyadh Armed Forces Hospital (RAFH)
With the growing need for establishing specialised centers for BMT procedures in the Kingdom of Saudi Arabia it was decided to provide this treatment at RAFH, as the second centre in addition to King Faissal Specialist Hospital in Riyadh, and this was made possible through the full and generous support of his Royal Highness Prince Sultan, Second Deputy Premier and Minister of Defense and Aviation and Inspector General and the Armed Forces Medical Administration. This service was offered to members of the Armed Forces and their dependents, and extended to benefit many other Saudi and non-Saudi patients suffering from serious hematological disorders. The first BMT procedure took place on 22nd May 1989, and until April 1996, 50 adults and 9 children underwent allogeneic BMT procedure from HLA compatible siblings plus only one autologous BMT. A list of the various indications is summarized in [Table 1].
Full assessment of recipient and donor was carried out prior to transplantation. The upper age limit of the recipient of allegeneic BMT was 45 years, and in case of acute leukaemia transplantation was done during first or subsequent remission. For chronic myelocytic leukaemia it was carried out during chronic phase in 15 patients, and in acute transformation in 3 patients. Histocompatibility testing for Class I and II human leucocyte (HLA) antigens was carried out on patient as well patient's parents and siblings to identify a fully compatible donor. Mixed lymphocyte cultures were done between patient and donor to confirm compatibility. Full medical, psychological and laboratory assessments were carried out on the patients and the donors to exclude the presence of any illness or infection which might be a risk factor for any of them. The nature of BMT procedure as well as the possible complications was fully explained to each patient and donor, and written consent forms were obtained prior to conditioning therapy. For adult donors, one unit of autologous blood was venesected 2-3 weeks prior to BMT in order to be given to the donor during the BM harvest procedure.
In 42 patients, cyclophosphamide and hyperfractionated total body irradiation (1440 cGy in 12 fractions) were used as pretransplant conditioning therapy. Busulphan and cyclophosphamide were used in 14 patients, and 4 patients with aplastic anemia were treated with cyclophosphamide ± lymphoid irradiation.
Bone Marrow Harvest and Processing
On the day of transplantation (Day 0), the donor was taken to the operating theatre, where under general anaesthesia bone marrow was aspirated bilaterally by two operators from posterior iliac crest posteriorly, and if necessary from anterior iliac crest as well aiming at a minimum nucleated cell count of 3 x 10 8 /kg of recipient weight. A bone marrow count was done during the procedure and in average 800-1000 ml of bone marrow was collected into a special bag containing heparinised tissue culture medium. If the patient and donor are ABO and Rh groups compatible, the marrow would be transfused unmanipulated, otherwise the marrow was processed for plasma or red cell depletion according to the degree of incompatibility. The bone marrow was subsequently transfused to the patient via a central venous catheter under close observation and monitoring.
Graft Versus Host Disease Prophylaxis
Cyclosporin A and methotrexate were used for graft versus host disease prophylaxis in all patients. Cyclosporin A was started Day-1 (3mg/kg daily intravenously) and subsequently changed to oral route when the patient was able to have oral intake, methotrexate was given at a dose of 15mg/ m 2 Day+1, and at 10/m 2 Day+3, +6 and + 11.
Severe pancytopenia developed in all patients for the first 2-3 weeks post-transplantation during which patients were susceptible to bacterial and fungal infections which required antibacterial, antifungal and antiviral (acyclovir) therapy. The majority of patients developed severe mucositis requiring parenteral opiate analgesic. All patients received total parenteral nutrition until they were able to take food orally. In addition, they received packed RBC's and platelet transfusions and white cell growth factors during the period of pancytopaenia. Following white cell recovery patients were given oral cotrimoxazole as prophylaxis against pneumocystis carinii infection.
The overall survival for the first 60 transplanted patient approached 50%. [Figure 1] shows the overall surival curves for the two largest groups of patients, chronic myeloid leukaemia and acute myeloid leukaemia, where the acturial five years survival was 67% and 47% respectively.
In October 1995 we finished the preparations for performing autologous bone marrow and peripheral blood stem cells transplantation which may be used for treating patients with solid tumours (e.g. lymphoma, breast carcinoma .... etc) as well as patients with leukaemia who are not suitable for allogeneic transplantation due to older age or donor unavailability. To perform this procedure, patients receive chemotherapy followed by granulocytecolony stimulating factor in order to mobilize stem cells into the circulation. Patients are then connected to a cell separator (Cobe-Spectra) in order to collect mononuclear cells which are then analysed by Flowcytometry in order to count the number of CD34 positive cells in the collected volume aiming at > 3 x 10 6 CD34 positive cell/kg body weight. These cells are then collected in a special bag, frozen and stored in liquid nitrogen for future use in performing autologous transplantation.