FIRST EXPERIENCE IN THE FIELD OF BONE MARROWTRANSPLANTATION AT THE ST.-PETERSBURG BMT CENTER
 
B.V.Afanasiev    

Zander AR et al. Gene Technology,Stem Cell and Leukemia ResearchNato Asi Series H: Cell Biology,
Vol 94Springer-Verlag, Berlin Heidelberg New York London

for St.-Petersburg BMT Center Team, 189646 St.-Petersburg Russia.


INTRODUCTION.

A significant proportion of patients, who did develop acute leukemia (AL) , chronic myelogenous leukemia (CML) , non Hodgkin-s (NHL) , Hodgkin-s disease (HD) , multiple myeloma (MM) , severe aplastic anemia (SAA) , myelodysplastic syndrom (MDS) and other malignancies may be cured with allogeneic (allo), autologous (auto) bone marrow and/or peripheral blood stem cell transplantation (PBSCT) .This article deals with first results of BMT and PBSCT performed at Petrov Research Institute of Oncology

Table 1. GENERAL DATA ABOUT BMT TRANSPLANTATION AT PETROV RESEARCH INSTITUTE OF ONCOLOGY




and St.-Petersburg City BMT Center between February 1989 and December 1994 (see table 1) . MATERIALS AND METHODS. Thirty-two alloBMT (16 children and 16 adults) , two second alloBMT (both in children), 3 syngeneic BMT, sixty-one autoBMT (9 children and 52 adults) , nine auto-PBSC and 6 auto-PBSC plus autoBMT transplantations were performed during the abovementioned time period. Patient characteristics of allo-and auto-BMT patients are shown in Tables 2 and 3.

Table 2. PATIENT CHARACTERISTICS FOR ALLOGENEIC BONE MARROW TRANSPLANTATION


Conditioning.regimens for allo- and syngeneic BMT included busulfan (Bu) plus cyclophosphamide (Cy) (Tutchka protocol) , Bu plus Cy plus VP-16 (Hamburg University protocol) .In SAA, we used Cy plus antithymocyte globulin (ATG) .

Table 3. PATIENT CHARACTERISTICS FOR AUTOLOGOUS BONE MARROW TRANSPLANTATION


For autoBM and PBSC transplantations, various conditioning regimens were applied, including CBV, or BEAM, or TACC, or high doses of Melphalan for MM, TBI plus Melphalan plus VP-16 for solid tumors. For PBSC mobilization and priming, G-CSF or GM-CSF have been used {NEUPOGEN "Roche" and LEUCOMAX "Sandoz") . Treatment efficiency of haematological malignancies can be predicted using some common prognostic signs which are assessed during primary examination, or prior to BMT. Therefore, we have analyzed the possible prognostic significance of such features as age, stage of disease, Karnovsky performance scores.


RESULTS AND CONCLUSION.

As seen from Table 1, an average of twenty-eight BMTs per year were performed at the St.- Petersburg BMT Center. Fig. 1 and 2 show survival rates in the patients with AL and in patients with AML treated with BMT. These results are in accordance with recent publications.


Fig.1 Survival rates in BMT patients with AL




Fig.2. Survival rates in BMT patients with AML

During the initial phase of transplantation program, we could not strictly stick to the common eligibility criteria, and included the patients with rather poor performance scores as well as with other contraindications for BMT. Hence, initial results are to be interpreted by considering an increased procedure-related mortality (Fig.3) . The significant relapse rates are the main problem at present time, due to changed inclusion criteria of patients.





Fig.3. Survival of BMT patients with different Karnovsky score

Reasons of mortality after allo- and auto-BMT included clinical relapses -30,3%, regimen-related toxicity -15,6%, acute GVHD -12,1%, fatal septic infections -12,1%. The most important prognostic factors for clinical outcomeof BMT were: patient age, Karnovsky score, and stage of the disease at the time of transplantation {Fig.3,4,5) .


Fig.4. Survival of BMT patients from different age groups




Fig.5 Survival of BMT patients with lymphomas (stage III vs. IV)

Overall survival of patients with a pre-treatment Karnovsky score of more than 70% were 62% {56 months follow-up) , in children 65% {48 months follow up), in patients with AL {CR state) 57 % {52 months follow-up) and and in patients with an early stage of malignancy 85 % (50 months follow-up) , thus being much higher compared with other groups(p< 0.05) .Highdosage chemotherapy followed by auto-BMT increased the overall survival rate in patients with aggressive multiple myeloma (MM), compared to conventional therapy, (62% during 32 months and 15% during 96 months, respectively, p < 0,05) , as shown in Fig. 6.






Fig.6 Survival of BMT patients with aggressive multiple myeloma (BMT vs.VAD protocol)




The preliminary experience with PBSC transplantation showed that this procedure is highly efficient, and in some instances it seems to be superior to BMT with respect to an accelerated recovery and decreased transfusion requirements (Tab.4) .


Table 4. BLOOD RECOVERY (days) AND REQUIREMENT FOR BLOOD PRODUCT TRANSFUSION
(number of transfusion days) AFTER BM, BM+PBSC AND PBSC TRANSPLANTATIONS


When summarizing the aforementioned data, a conclusion may be drawn, that the latest experience of St.-Petersburg BMT Center yielded sufficient clinical results which are in good agreement with results of multicentric studies. One of the most promising approaches will be the wider use of intensive chemo/radiation therapy employing hematopoietic stem cells transplantation. Treatment should be started at the earliest stage of malignancy, especially in patients with poor prognosis.


ACKNOWLEDGEMENTS

We would like to express our deep gratitude to Prof. Axel Zander and to all his colleagues at BMT Center, University Hospital Eppendorf (Hamburg), for valuable aid, clinical consulting and stimulating discussions.