Effects of bone marrow fibrosis and angiogenetic structure on autologous hematopoietic stem cell engraftment
Öz
Purpose: Hematopoietic stem cell (HSC) engraftment is influenced by many factors. We investigated the effects of bone marrow fibrosis and angiogenetic structure on engraftment in patients with hematological malignancies.
Materials and Methods: Data were collected from 34 patients (20 males and 14 females) who underwent autologous HSC transplantation. Bone marrow myelofibrosis was graded from 0 to 3, angiogenesis was quantified using a stereological method in the most recent bone marrow biopsy before the transplantation. Patients were categorized into two groups according to intensity of angiogenesis parameters.
Results: Half of the patients had fibrosis and majority had multiple myeloma (73.5%). Eleven patients had grade 1, six had grade 2 myelofibrosis. The engraftment day (ED) for platelets and erythrocytes was significantly different between the grade 2 fibrosis and non-fibrosis groups. VSD and NVES levels were significantly higher in the grades 1 and 2 fibrosis groups than the no fibrosis group. While the overall survival time was shorter in the grade 2 fibrosis group than the others, the difference was not statistically significant.
Conclusion: Bone marrow fibrosis was found to be independent risk factor. It may have a negative effect on platelet and erythrocyte engraftment time of autologous transplantation process but this effect does not influence survival.
Anahtar Kelimeler
Bone marrow fibrosis angiogenesis autologous transplantation multiple myeloma
Kaynakça
- 1. Ippoliti C, Przepiorka D, Giralt S, Andersson BS, Wallerstein RO, Gutterman J et al. Low-dose non-glycosylated rhGM-CSF is effective for the treatment of delayed hematopoietic recovery after autologous marrow or peripheral blood stem cell transplantation. Bone Marrow Transplant. 1993;11:55–9.
- 2. Crump M, Couture F, Kovacs M, Saragosa R, McCrae J, Brandwein J et al. Interleukin-3 followed by GM-CSF for delayed engraftment after autologous bone marrow transplantation. Exp Hematol. 1993;21:405–10.
- 3. Khwaja A, Goldstone AH, Linch DC. Delayed neutrophil recovery after BEAM chemotherapy and autologous bone marrow transplantation for lymphoma is not associated with increased mortality from infection. Bone Marrow Transplant. 1995;15:313–5.
- 4. Lichtman MA. The ultrastructure of the hemopoietic environment of the marrow: a review. Exp Hematol. 1981;9:391-410.
- 5. Weiss L. The hematopoietic microenvironment of the bone marrow: an ultrastructural study of the stroma in rats. Anat Rec. 1976;186:161-84.
- 6. Fliedner TM, Graessle D, Paulsen C, Reimers K. Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure. Cancer Biother Radiopharm. 2002;17:405-26.
- 7. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841-6.
- 8. Lord BI, Testa NG, Hendry JH. The relative spatial distributions of CFUs and CFUc in the normal mouse femur. Blood. 1975;46:65-72.
- 9. Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz O, Terhorst C, Morrison SJ. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005;121:1109-21.
- 10. Shen Q, Goderie SK, Jin L, Karanth N, Sun Y, Abramova N et al. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science. 2004;304:1338-40.
- 11. Shackney SE, Ford SS, and Wittig AB. Kinetic-microarchitectural correlations in the bone marrow of the mouse. Cell Tissue Kinet. 1975;8:505-16.
- 12. Shirota T and Tavassoli M, Cyclophosphamide-induced alterations of bone marrow endothelium: implications in homing of marrow cells after transplantation. Exp Hematol. 1991;19:369-73.
- 13. Tavassoli M. Hemopoietic endothelium, incognito. Exp Hematol. 1992;20:386-87.
- 14. Nilsson SK, Simmons PJ, and Bertoncello I. Hemopoietic stem cell engraftment. Exp Hematol. 2006;34:123-9.
- 15. Barth PJ, Weingartner K, Köhler HH, Bittinger A. Assesment of vascularization in prostatic carcinoma: a morphometric investigation. Hum. Pathol. 1996;27:1306-10.
- 16. Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90:1128-32.
- 17. Haas R, Witt B, Möhle R, Goldschmidt H, Hohaus S, Fruehauf S et al. Sustained long-term hematopoiesis after myeloablative therapy with peripheral blood progenitor cell support. Blood. 1995;85:3754-61.
- 18. Bensinger WI, Longin K, Appelbaum F, Rowley S, Weaver C, Lilleby K et al. Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): an analysis of factors correlating with the tempo of engraftment after transplantation. Br J Haematol. 1994;87:825-31.
- 19. van der Wall E, Richel DJ, Holtkamp MJ, , Slaper-Cortenbach IC, van der Schoot CE, Dalesio O et al. Bone marrow reconstitution after high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation: effect of graft size. Ann Oncol. 1994;5:795-802.
- 20. Weaver CH, Hazelton B, Birch R, Palmer P, Allen C, Schwartzberg L et al. An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy. Blood. 1995;86:3961-9.
- 21. Mounier N, Larghero J, Manson J, Brice P, Madelaine-Chambrin I, Brière J et al. Long term hematologic recovery after autologous stem cell transplantation in lymphoma patients: impact of the number of prefreeze and post-thaw CD34+ cells. Bull Cancer. 2005;92:E31-8.
- 22. Hohaus S, Goldschimidt H, Ehrhardt R, Haas R. Successful autografting following myeloablative conditioning therapy with blood stem cells mobilized by chemotherapy plus rhG-CSF. Exp Hematol. 1993;21:508-14.
- 23. Soll E, Massumoto C, Clift RA, Buckner CD, Appelbaum FR, Storb R et al. Relevance of marrow fibrosis in bone marrow transplantation: a retrospective analysis of engraftment. Blood. 1995;86:4667-73.
- 24. Scott BL, Storer BE, Greene JE, Hackman RC, Appelbaum FR, Deeg HJ. Marrow fibrosis as a risk factor for posttransplantation outcome in patients with advanced myelodysplastic syndrome or acute myeloid leukemia with multilineage dysplasia. Biol Blood Marrow Transplant. 2007;13:345-54.
- 25. Vacca A, Ribatti D, Presta M, Minischetti M, Iurlaro M, Ria R et al. Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood. 1999;93:3064-73.
- 26. Perez-Atayde AR, Sallan SE, Tedrow U, Connors S, Allred E, Folkman J. Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am J Pathol. 1997;150:815-21.
- 27. Reilly J.T Idiopathic myelofibrosis: pathogenesis, natural history and management. Blood Rev. 1997;11:233-42.
- 28. Pruneri G, Bertolini F, Soligo D, Carboni N, Cortelezzi A, Ferrucci PF et al. Angiogenesis in myelodysplastic syndromes. Br J Cancer. 1999;81:1398-1401.
- 29. Suyanı E, Akı SZ, Yegin ZA, Ozkurt ZN, Altındal S, Akyürek N et al. The impact of bone marrow fibrosis on the outcome of hematopoietic stem cell transplantation. Transplant Proc. 2010;42:2713-9
Öz
Amaç: Birçok faktör hematopoetik kök hücre (HKH) engraftmanını etkiler. Bu çalışmada hematolojik kanseri olan hastalarda kemik iliğindeki myelofibrozis ve anjiogenezisin engraftman üzerine etkisi araştırılmıştır.
Gereç ve Yöntem: Otolog kök hücre nakli yapılan 34 hasta (20 erkek, 14 kadın) verileri değerlendirildi. Nakilden önceki son kemik iliğindeki fibrozis 0-3 arasında derecelendirildi, anjiogenezis stereolojik metod ile ölçüldü. Hastalar anjiogenezis parametrelerinin yoğunluğuna göre de iki gruba ayrıldı.
Bulgular: Hastaların çoğunluğu (%73.5) multipl myelom idi ve yarısında fibrozis saptandı. On bir hasta derece 1, 6 hasta derece 2 fibrozise sahipti. Trombosit ve eritrosit engraftman günleri açısından derece 2 fibrozisi olan grupla fibrozis saptanmayan grup arasında istatistiksel anlamlı farklılık vardı. Derece 1 ve 2 fibrozis gruplarında fibrozisi olmayanlara göre VSD ve NVES düzeyleri anlamlı olarak yüksekti. Toplam yaşam derece 2 fibrozisi olan grupta daha düşük olmakla birlikte istatistiksel anlamlılık yoktu.
Sonuç: Kemik iliği myelofibrozisinin bağımsız bir risk faktörü olduğu saptanmıştır. Bunun toplam yaşamı etkilemeden otolog nakil sürecinde trombosit ve eritrosit engraftmanı üzerine negatif etkisi olabilir. Fibrozisin derecesi ile doğru orantılı olarak artmış anjiogenezis arasındaki ilişkiyi açıklamak için ileri çalışmalar gereklidir.
Anahtar Kelimeler
Kemik iliği fibrozisi anjiogenezis otolog transplantasyon multipl myelom
Kaynakça
- 1. Ippoliti C, Przepiorka D, Giralt S, Andersson BS, Wallerstein RO, Gutterman J et al. Low-dose non-glycosylated rhGM-CSF is effective for the treatment of delayed hematopoietic recovery after autologous marrow or peripheral blood stem cell transplantation. Bone Marrow Transplant. 1993;11:55–9.
- 2. Crump M, Couture F, Kovacs M, Saragosa R, McCrae J, Brandwein J et al. Interleukin-3 followed by GM-CSF for delayed engraftment after autologous bone marrow transplantation. Exp Hematol. 1993;21:405–10.
- 3. Khwaja A, Goldstone AH, Linch DC. Delayed neutrophil recovery after BEAM chemotherapy and autologous bone marrow transplantation for lymphoma is not associated with increased mortality from infection. Bone Marrow Transplant. 1995;15:313–5.
- 4. Lichtman MA. The ultrastructure of the hemopoietic environment of the marrow: a review. Exp Hematol. 1981;9:391-410.
- 5. Weiss L. The hematopoietic microenvironment of the bone marrow: an ultrastructural study of the stroma in rats. Anat Rec. 1976;186:161-84.
- 6. Fliedner TM, Graessle D, Paulsen C, Reimers K. Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure. Cancer Biother Radiopharm. 2002;17:405-26.
- 7. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841-6.
- 8. Lord BI, Testa NG, Hendry JH. The relative spatial distributions of CFUs and CFUc in the normal mouse femur. Blood. 1975;46:65-72.
- 9. Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz O, Terhorst C, Morrison SJ. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005;121:1109-21.
- 10. Shen Q, Goderie SK, Jin L, Karanth N, Sun Y, Abramova N et al. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science. 2004;304:1338-40.
- 11. Shackney SE, Ford SS, and Wittig AB. Kinetic-microarchitectural correlations in the bone marrow of the mouse. Cell Tissue Kinet. 1975;8:505-16.
- 12. Shirota T and Tavassoli M, Cyclophosphamide-induced alterations of bone marrow endothelium: implications in homing of marrow cells after transplantation. Exp Hematol. 1991;19:369-73.
- 13. Tavassoli M. Hemopoietic endothelium, incognito. Exp Hematol. 1992;20:386-87.
- 14. Nilsson SK, Simmons PJ, and Bertoncello I. Hemopoietic stem cell engraftment. Exp Hematol. 2006;34:123-9.
- 15. Barth PJ, Weingartner K, Köhler HH, Bittinger A. Assesment of vascularization in prostatic carcinoma: a morphometric investigation. Hum. Pathol. 1996;27:1306-10.
- 16. Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90:1128-32.
- 17. Haas R, Witt B, Möhle R, Goldschmidt H, Hohaus S, Fruehauf S et al. Sustained long-term hematopoiesis after myeloablative therapy with peripheral blood progenitor cell support. Blood. 1995;85:3754-61.
- 18. Bensinger WI, Longin K, Appelbaum F, Rowley S, Weaver C, Lilleby K et al. Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): an analysis of factors correlating with the tempo of engraftment after transplantation. Br J Haematol. 1994;87:825-31.
- 19. van der Wall E, Richel DJ, Holtkamp MJ, , Slaper-Cortenbach IC, van der Schoot CE, Dalesio O et al. Bone marrow reconstitution after high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation: effect of graft size. Ann Oncol. 1994;5:795-802.
- 20. Weaver CH, Hazelton B, Birch R, Palmer P, Allen C, Schwartzberg L et al. An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy. Blood. 1995;86:3961-9.
- 21. Mounier N, Larghero J, Manson J, Brice P, Madelaine-Chambrin I, Brière J et al. Long term hematologic recovery after autologous stem cell transplantation in lymphoma patients: impact of the number of prefreeze and post-thaw CD34+ cells. Bull Cancer. 2005;92:E31-8.
- 22. Hohaus S, Goldschimidt H, Ehrhardt R, Haas R. Successful autografting following myeloablative conditioning therapy with blood stem cells mobilized by chemotherapy plus rhG-CSF. Exp Hematol. 1993;21:508-14.
- 23. Soll E, Massumoto C, Clift RA, Buckner CD, Appelbaum FR, Storb R et al. Relevance of marrow fibrosis in bone marrow transplantation: a retrospective analysis of engraftment. Blood. 1995;86:4667-73.
- 24. Scott BL, Storer BE, Greene JE, Hackman RC, Appelbaum FR, Deeg HJ. Marrow fibrosis as a risk factor for posttransplantation outcome in patients with advanced myelodysplastic syndrome or acute myeloid leukemia with multilineage dysplasia. Biol Blood Marrow Transplant. 2007;13:345-54.
- 25. Vacca A, Ribatti D, Presta M, Minischetti M, Iurlaro M, Ria R et al. Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood. 1999;93:3064-73.
- 26. Perez-Atayde AR, Sallan SE, Tedrow U, Connors S, Allred E, Folkman J. Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am J Pathol. 1997;150:815-21.
- 27. Reilly J.T Idiopathic myelofibrosis: pathogenesis, natural history and management. Blood Rev. 1997;11:233-42.
- 28. Pruneri G, Bertolini F, Soligo D, Carboni N, Cortelezzi A, Ferrucci PF et al. Angiogenesis in myelodysplastic syndromes. Br J Cancer. 1999;81:1398-1401.
- 29. Suyanı E, Akı SZ, Yegin ZA, Ozkurt ZN, Altındal S, Akyürek N et al. The impact of bone marrow fibrosis on the outcome of hematopoietic stem cell transplantation. Transplant Proc. 2010;42:2713-9
Ayrıntılar
| Konular | Sağlık Kurumları Yönetimi |
|---|---|
| Bölüm | Araştırma |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Eylül 2017 |
| Kabul Tarihi | 23 Şubat 2017 |
| Yayımlandığı Sayı | Yıl 2017 Cilt: 42 Sayı: 3 |
