عنوان : سرطان ثانويه در بيماران مبتلا به هوجكين دربيمارستان حضرت علي اصغر (ع)

نويسنده ، نويسندگان : شهلا انصاري – پروانه وثوق

نشاني : تهران ، بيمارستان حضرت علي اصغر (ع)

مقدمه و اهداف :

بيماري هوجكين يكي از سرطانهاي شايع دوران كودكي است كه در صورت تشخيص و معالجه موثر قابل درمان است . يكي از موانع مهم در بهبود اين بيماران بروز سرطان ثانويه است ، كه چندين سال پس از درمان بيماران مبتلا به هوجكين ظاهر مي شود . علت ايجاد آن را مربوط به روش درماني به كار رفته ( شيمي درماني و راديوتراپي ) شروع درمان ، جنس ، نقص ايمني حاصل از آن بيماري مي دانند .

روش اجرا :

مطالعه بيماران مبتلا به بيماري هوجكين كه در ده سال گذشته در بيمارستان حضرت علي اصغر درمان شده بودند .

يافته هاي پژوهش :

از 228 بيمار هوجكين درمان شده در اين مركز چهار مورد سرطان ثانويه بروز كرده كه سه مورد آن تومورهاي توپر و يك مورد سرطان خون بوده است .

نتايج :

سه مورد بيماري كه مبتلا به تومور توپر شدند ، درمان اوليه راديوتراپي گرفته بودند و به ترتيب 8-17-19 سال بعد مبتلا به تومور توپر شده اند ، كه يك مورد تومور مغزي منجر به مرگ شد . دو مورد سرطان تيروئيد كه با تيروئيد كتومي بهبود يافته و در حال حاضر زنده هستند ، و يك مورد 6 سال بعد از شيمي درماني هاي مكرر به دليل عود مبتلا به سرطان خون شده كه منجر به فوت گرديد . در اين مركز به دليل كاربرد محدود راديوتراپي شيوع سرطان ثانويه نسبت به مراكز ديگر كمتر ديده مي شود .

Title of Article : Second malignancy in-patients with Hodgkin diseases in Ali Asghar Children Hospital

Author(s):Ansari.Sh – Vosogh.P

Address : Tehran – Ali Asghar Children Hospital 19166

Introduction & Objectives :

Hodgkin disease is one of the most common childhood malignancy that with correct diagnosis and effective treatment is curable . Hower concern fof the risk of long term complication has resulted in a number of trials evaluate reduction of therapy . Causes of second malignancy are related to kinds of therapies ( radiotherapy-chemotherapy) , age of patients in first treatment , sex and immunological deficits with disease .

Method :

Studied in patients with Hodgkin’s diseases treated in Ali Asghar children Hospital in ten years ago .

Results :

In 228 patients with Hodgkin diseases 4 cases with second malignancy were presented . 3 cases presented with solid tumor and one case was leukemia (AML) .

Discussion & Conclusion :

3 case that first treared with radiotherapy after 8-18-19 years later presented with solid tumor , one case died from brain tumor and two cases presented with thyroid cancer had thytoidectomy for recurrent disease developed leukemia and died from AML . Because in the center radiotherapy is testricted , the incidence of decond malignancy is less than other centers .

In addition , the phenotype properties of expanded cells were studied by dual-color flow cytometry with a panel of monoclonal antibodies including , CD34,CD33,CD45,CD14 .

Results :

Apheresis samples were processed for CD34⁺ selection using the avidin-immuno-affinity column to enrich CD34⁺ Peripheral blood progenitor cells . After separation , purity of CD34⁺ cells was more than 85% ( range 52 to 93% )

The ecpansion of total cells in suspension cultures was increased in the presence of the cytokine combination IL-3,G-CSF,GM-CSF,SCF as compared to controls (680 fold ) .

The median increase in clonogeneic progenitor cells was 45-fold for BFU-E, 55-fold for CFU-GEMM, and 193-fold for CFU-GM after 7 days of suspendion cutur with SCF,IL-3, G-CSF , GM-CSF , and epo . The number of CD34⁺ cells decreased from 85% to 42% by day 7 .

The number of cells expressing CD33 increased rapidly , with more than 80 % being CD33⁺ cells by day 7 . Cells generated in culture progressively acquired CD14 antigen with 40% of cells being CD14⁺ on day 7 and 85% on day 14 .

In patients given only first line chemotherapy a median expansion of 412 fold for nuclear cells , 201 fold for CFU-GM, 60 fold for BFU-E, 68 fold for CRU-GEMM was achived . In contrast , patients treated with second or therd line chemotherapy prior to PBSC mobilisation has a median of 140 fold for nuclear cells , 114 fold for CFU-GM, 16 for BFU-E, 27 fold for CFU-GEMM .

Discussion & conclusion :

This study confirms the expansion of peripheral blood progenitor cell number and clonogeneic growth faxtors , SCF, IL-3 , G-XSF , CM-CSF , and epo . However , a rapid differentiation of early hematopoetic cells was observed with the culture conditions used .

Title of Article : Ex-vivo Expansion of CD34-selected peripheral blood progenitor cells .

Author : Fariborz Elahi , Hong Zhu, Paul Hocker , Nina Worel,Felix Keil,Barbara

Schneider , Klaus Lechner , Hildegard Theresia Greinix

Adress:Department of Internal Medicing , Bone Marrow Transplantation Unit , University

Of Vienna , Austria

Tel : 43-1-40400 4412

Introduction & Objectives :

We used expansion strategies with different cytokine combinations to increase the number of hematopoietic progenitor cells after peripheral blood stem cell (PBSC) collection for clinical use after high-dose chemotherapy . These il-vitro studies are the prerequisite for large scale expansion . Furthermore ex vivo expansion in suspension cultures might reduce the possibility of tumor cell contamination in patients with malignant disease .

Method :

PBSC were obtaired ftom 25 patents with solid tumors or hematologic malignances .

After leukapheresis , CD34⁺ cells were enriched by immunoadsorption using the Cell pto cdumn and subsequently expanded in suspension culture at 2 to 5x10³ cells/ml for 7 to 14 days in the presense of various recombinant human growth factors: Erythropoetin (EPO) (5U/ml ) , Interleukin 3 (IL-3) (100ng/ml) , Grnulocyte Maktophage-colony stimulating factor (GM-CSF) (100ng/ml), Granulocyte Makrophage-colony stimulating factor (G-CSF) (100ng/ml ) , Stem Cell factor (SCF) (50ng/ml) .

Then they were analyzed for their capacity to form clonogeneic cells in methylcellulose assay of different lineages including colony forming unit- Granulocyte Maktophage (CFU-GM) , Burst forming unit (BFU-E) and colony forning unit Granulocyte Erythrocyte Monocyte Megakayocyte (CFU-GEMM ) .

Summary :

Expansion of LTC –IC by IL-10+IL-3+SCF has not been shown so far . In summary , our in vitro model allows expansion of LTC-IX if vompared with the input of progitor cells without extensive stem cell manipulation . This should be an attractive model for in vitro purging , gene transfer of expansion of stem cells to allow rapid engraftment after myeloablative chemotherapy .

Title : Ecpansion of colony forming cells of high proliferation potential and long term culture initiating cells by IL-10 , SCF and IL-3 in vitro

Authors : Fariborz Hahi , Felix Keil , Hildegard T . Greinix , Gethard Fritsch , Morbert Louda , Andress L . Petzer , Erika Prinz , Thomas Wagne , peter Kahls Klaus Lechner and Klaus Geissler

Adress : Department of Internal Medicine , Bone Marrow Transplantation Unit ,

University of Vienna , Autria , Tel : 43-1-404000 4412

Introduction & Objective :

Ex vivo expansion of stem cells mayshorten hematopoietic regeneration after myelooablative chemoradiotheray , increases target cells for gene therapy and may improve purging of temcell products .

Methods :

Bone marrow (BM) cells were incubated for 1 week in suspension culture with and without IL-10 , IL-3 and SCF . As long term culture initiating cells (C-IC) represent early henatopoietic progenitors in vivo these cells were quantified at initiation and after 1 week culture period in a Limiting dution assays . Additionally immunophenotyping of cells before and after culture was perfomed .

Results :

In six experiments BM cells cultured one week with IL-10 , IL-3 and SCF showed a significant increase with almos doubling LTC-IC if compared with BM cells per-expansion . Additionally , an anincreased proliferative capacity of LTC-IC was achieved with a 7 fold increase of committed colony forming cells (CFC) and a 10 fold proliferation of high proliferative potential CFC , Immunophenotyping revealed a 7 fold increase of CD34 positive CD45RA negative cells in IL-10+IL-3+SCF stimulated suspension cultures . In unstimulated cultures no LTC-IC were maintained after one week .