Ultrastructural Observations in Therapy-Related Panmyelosis

  • Robert W. McKenna
  • Janet L. Parkin
  • Richard D. Brunning
Part of the Developments in Oncology Series book series (DION, volume 14)


Acute nonlymphocytic leukemia occurring in individuals having received alkylating agent chemotherapy and/or radiotherapy is a well-recognized complication of treatment of hematologic and nonhematologic malignancies and certain nonneoplastic disorders [1–9]. The incidence of acute leukemia in these patients is not well established but appears to be related to the intensity of therapy and age of the patient [10–12]. The interval from the commencement of the treatment of the primary disease to the recognition of the secondary leukemia varies considerably; in the patients studied in this institution it has ranged from 25 to 182 months, with a median interval of 66 months. Response to treatment for the therapy-related leukemias has generally been poor and survival has been shorter than for non-therapy-related acute myelogenous leukemia [13–15].


Uranyl Acetate Acute Leukemia Lead Citrate Acute Myelogenous Leukemia Mast Cell Granule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Court-Brown WM, Doll R. Mortality from cancer and other causes after radiotherapy for ankylosing spondylitis. Br Med J 2: 1327–1332, 1965.CrossRefGoogle Scholar
  2. 2.
    Smit CGS, Meylcr L Acute myeloid leukemia after treatment with cytostatic agents. Lancet 2: 671–672. 1970.PubMedCrossRefGoogle Scholar
  3. 3.
    Davis HL. Prout MN. McKenna PJ, Cole DR, Korbirz BC. Acute leukemia complicating metastatic breast cancer. Cancer 31: 543–546. 1973.PubMedCrossRefGoogle Scholar
  4. 4.
    Kyle RA. Pierre RV. Bayrd ED. Multiple myeloma and acute leukemia associated with alkylating agents. Arch Intern Med 135: 185–192. 1975.PubMedCrossRefGoogle Scholar
  5. 5.
    Rosner R. Grunwald H. Hodgkin’s disease and acute leukemia: Report of eight cases and review of literature. Am J Med 58: 339–353, 1975.PubMedCrossRefGoogle Scholar
  6. 6.
    Tehernia G. Mielot F. Subtil E, Parmentier C. Acute myeloblasts leukemia after immunodepressive therapy for primary non- malignant disease. Blood Cells 2: 67–78, 1976.Google Scholar
  7. 7.
    Cadman EC. Capizzi RL. BerunoJR. Acute non lymphocytic leukemia, a delayed complication of Hodgkin’s disease therapy: Analysis of 109 cases. Cancer 40:1280–1296, 197 7.Google Scholar
  8. 8.
    Collins AJ, Bloomfield CD, Peterson BA. McKenna RW. Acute non lymphocytic leukemia in patients with nodular lymphoma. Cancer 40: 1748–1754, 1977.PubMedCrossRefGoogle Scholar
  9. 9.
    DeBock RFK. Peetermans ME. Leukemia after prolonged use of melphalan for non-malignant disease. Lancet 1: 1208–1209, 1977.CrossRefGoogle Scholar
  10. 10.
    Einhorn N. Acute leukemia after chemotherapy (melphalan). Cancer 4l: 444–447, 1978.CrossRefGoogle Scholar
  11. 11.
    Bergsagel DE, Bailev AJ, Langley GR. Mac Donald RN, White DF. Miller AB. The chemotherapy of plasma cell myeloma and the incidcnce of acute leukemia. New Engl J Med 301: 743–748. 1979.PubMedCrossRefGoogle Scholar
  12. 12.
    Valagussa P. Santora A, Kenda RE, Fossata Bellani F. Franchi F. Banh A, Rilke F, Bonadonna G. Second malignancies in Hodgkin’s disease: A complication of certain forms of treatment Br Med J 1: 216–226, 1980.CrossRefGoogle Scholar
  13. 13.
    Bukowski RM, Weick JK. Reimer RR. Groppe GW, Hewlett JS. Characteristics of acute leukemia in patients with non- malignant diseases receiving alkylating agent therapy. Blood (suppl) 50: 185. 1977 (abstract).Google Scholar
  14. 14.
    Coleman CM. Williams CJ, Flint A, Glatstein EJ, Rosenberg SA. Kaplan HS. Hematologic neoplasia in patients treated for Hodgkin’s disease. New Engl J Med 297: 1249–1252, 1977.PubMedCrossRefGoogle Scholar
  15. 15.
    Foucar K. McKenna RW, Bloomfield CD, Bowers TK, Brunning RD. Therapy related leukemia: A panmyelosis. Cancer 43: 1285–1296, 1979.PubMedCrossRefGoogle Scholar
  16. 16.
    Khaleeli M. Keane WM. Lee GR. Sideroblastic anemia in multiple myeloma: A preleukemic change. Blood 41: 17–25. 1973.PubMedGoogle Scholar
  17. 17.
    Vardiman JW. Golomb HM. Rowley JD. Variakojis D. Acute nonlymphocytic leukemia in malignant lymphoma: A morphologic study. Cancer 42: 229–242, 1978.PubMedCrossRefGoogle Scholar
  18. 18.
    Cardamone JM. Kimmerle Rl. Marshall EY. Development of acute crythroieukemia in B-cell immunoproliferative disorders after prolonged therapy with alkylating agents. Am J Med 57: 836–842, 1974.PubMedCrossRefGoogle Scholar
  19. 19.
    Kyle RA. Pierre RV. Bayrd ED. Multiple myeloma and acute myelomonocvtic leukemia. New Engl J Med 283: 1121–1125. 1970.PubMedCrossRefGoogle Scholar
  20. 20.
    McKenna RW. Parkin JL, Foucar K. Brunning RD Ultrastructural characteristics of therapy related acute nonlymphocytic leukemia: Evidence for a panmyelosis. Cancer 48:725–737, 1981.Google Scholar
  21. 21.
    Rowley JD, Golomb HM, Vardiman J. Nönrandom chromosomal abnormalities in acute non-lymphocytic leukemia in patients treated for Hodgkin’s disease and non Hodgkin lymphomas. Blood 50: 759–770. 1977.Google Scholar
  22. 22.
    Thiery J P. Aurias A, Dumont J, Mazabraud A, Trupet P. Acute nonlymphocytic leukemias following chemotherapy: Ultrastructural study of erythroblastic cell line and discussion of nuclear anomalies. Blood Cells 7: 341–356, 1981.PubMedGoogle Scholar
  23. 23.
    Maldonado JE, Maigne J, Lecoq D. Comparative electron microscopic study of the erythrocytic line in refractory anemia (preleukemia) and myelomonocytic leukemia. Blood Cells 2: 167–185, 1976.Google Scholar
  24. 24.
    Huhn D, Kaboth W, Schmalzl F. DiGuglielmo-syndrom: Klinische zytochemische, elektronenmikroskopische befunde. Dtsch Med Woch 98: 355–360, 1973.CrossRefGoogle Scholar
  25. 25.
    Kass L, Schnitzer B. Refractory anemia. Springheld. III.; Charles C Thomas. 1975, p. 148.Google Scholar
  26. 26.
    Ahearn MJ, Trujillo JM, Cork A, Fowler A, Hare.IS. The association of nuclear blebs with aneuploidy in human acute leukemia. Cancer Res 34: 2887–2896, 1974.PubMedGoogle Scholar
  27. 27.
    Schumacher HR, Szekely IE, Park SA, Fisher DR. Ultrastructural studies on the acute leukemic lymphoblast. Blut 27. 396–406, 1973.CrossRefGoogle Scholar
  28. 28.
    McKenna RW, Parkin J. Brunning RD: Morphologic and ultrastructural characteristics of T-cell acute lymphoblastic leukemia. Cancer 44: 1290–1297, 1979.PubMedCrossRefGoogle Scholar
  29. 29.
    Frisch B. Lewis SM, Sherman D. The ultrastructure of dyserythropoiesis in aplastic anemia. Br J Haematol 29: 545–552, 1975.PubMedCrossRefGoogle Scholar
  30. 30.
    Wickramasinghe SN, Bush V. Electron microscope and high resolution autoradiographic studies of megaloblastic erythropoiesis. Acta Haematol 57: 1–14, 1977.PubMedCrossRefGoogle Scholar
  31. 31.
    Hay hoe FGJ, Cawley JC. Acute leukemia: Cellular morphology, cytochemistry and fine structure. Clin Haematol 1: 49–94, 1972.Google Scholar
  32. 32.
    Lewis SM, Verwilghen RL. Dyserythropoiesis and dyserythropoietic anemias. In: vol 8. Brown ED. ed. Progress in hematology. New York: Grune & Stratton, 1973; pp. 99–129.Google Scholar
  33. 33.
    Dvilansky A, Sukenik S, Stern J, Djaldetti M. Congcnical dyserythropoietic anemia with ultrastructure findings compatible with both tvpes 1 and II. Acta Haematol 52: 161–168, 1974.PubMedCrossRefGoogle Scholar
  34. 34.
    Rozman C, Woessner S, Ribas-Mundo M, San Miguel JG, Vives-Corrons JL, Vives- Puiggros, Nomdedeu B. Congenital dyserythropoietic anemia type II: Clinical and ultrastructural study. Acta Haematol 52: 312–319. 1974.PubMedCrossRefGoogle Scholar
  35. 35.
    Lewis SM. Frisch B. Congenital dyserythropoietic anemias: Electron microscopy. In Porter R. Fitzsimons DW. eds. Congenital disorders of erythropoiesis. Ciba Foundation Symposium 37 (new series). Amsterdam: Elsevier, 1976, pp. 171–203.Google Scholar
  36. 36.
    Sansone G. A new type of congenital dyserythropoietic anaemia. Br J Haematol 39: 537–543. 1978.PubMedCrossRefGoogle Scholar
  37. 37.
    Wickramasinghe SN. Pathophysiology of the proliferation and Cytodiffcrentiation of megaloblasts. In: Lewis SM, Verwilghen RL, eds. Dyserythropoiesis. London: Academic Press, 1977, pp. 88–91.Google Scholar
  38. 38.
    Kent G. Minick OT, Volini Fl, Orfei F.. Autophagic vacuoles in human red cells. Am J Pathol 48: 831–858, 1966.PubMedGoogle Scholar
  39. 39.
    Heynen MJ: Experimental dyserythropoiesis. In: Lewis SM, Verwilghen RL, eds. Dyserythropoiesis. London: Academic Press, 1977, p. 324.Google Scholar
  40. 40.
    Seman G, Seman C. Electron microscopic search for virus particules in patients with leukemia and lymphoma. Cancer 22: 1033–1045. 1968.PubMedCrossRefGoogle Scholar
  41. 41.
    Cawley J, Karpas A. The ultrastructural demonstration of virus-like particles in human leukemic cells. Eur I Cancer 10: 559–562, 1974.CrossRefGoogle Scholar
  42. 42.
    Foa C. Foa J, Carcassone Y. Morphologic study of virus-like particles in a case of acute leukemia. Cancer 37: 1718–1724, 1976.PubMedCrossRefGoogle Scholar
  43. Parkin J. Brunning RD. Tubular complexes of endoplasmic reticulum in myeloblasts of acute myelogenous leukemia. Ultrastruct Pathol 1: 55–65, 1980.PubMedCrossRefGoogle Scholar
  44. 44.
    Seman G. Ultrastructural study of B- bodies in leukapheresed cells of patients with acute leukemia. Oncol 38: 201–209. 1981.CrossRefGoogle Scholar
  45. 45.
    Grimley P. Schaff Z. Significance of tubuloreticular inclusions in the pathobiology of human diseases. Pathobiol Annu 11: 221–257. 1976.Google Scholar
  46. 46.
    Fujinaga S. Fine structure and development of Auer bodies. Kyushu J Med Sci 15: 59 - 68. 1964.PubMedGoogle Scholar
  47. 47.
    Freeman JA. Origin of Auer bodies. Blood 27: 499–510. 1966.PubMedGoogle Scholar
  48. 48.
    McDuffie NG. Crystalline patterns in Auer bodies and specific granules of human leukocytes. J Microscopic 6: 321–330. 1967.Google Scholar
  49. 49.
    Efrati P, Nir E, Kaplan H. Dvilanski A. Pseudo-Chediak-Higash: anomaly in acute myeloid leukaemia: An electron microscopical study. Acta Haematol 61: 264–271, 1979.PubMedCrossRefGoogle Scholar
  50. 50.
    Tulliez M, Vernant JP, Breton-Gorius J, Imbert M. Sultan C. Pseudo-Chediak- Higashi anomaly in a case of acute myeloid leukemia: Electron microscopic studies. Blood 54:863–871, 1979-Google Scholar
  51. 51.
    Parmley RT, Dahl GV, Austin RL, Gauthier PA, Denys FR. Ultrastructural and cytokinetics of leukemic myeloblasts containing giant granules. Cancer Res 39:3834–3844, 1979-Google Scholar
  52. 52.
    Dittman WA, Kramer RJ, Bainton DF. Electron microscopic and peroxidase cytochemical analysis of pink pseudo-Chediak- Higashi granules in acute myelogenous leukemia. Cancer Res 40: 4473–4481, 1980.PubMedGoogle Scholar
  53. 53.
    Graham R, Karnovsky M. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: Ultrastructural cytochemistry by a new technique. J Histochem Cytochem 14: 291–302, 1966.PubMedCrossRefGoogle Scholar
  54. 54.
    Breton-Gorius J, Coquin Y, Vilde JL, Dreyfus B. Cyrochemical and ultrastructural studies of aberrant granules in the neutrophils of two patients with myeloperoxidase deficiency during a preleukemic state: Relationship to abnormal bactericidal activity. Blood Cells 2: 187–206, 1976.Google Scholar
  55. 55.
    Breton-Gorius J. Abnormalities of granulocytes and megakaryocytes in preleukemic syndromes. In: Schmalzl F, Hellriegel KP, eds. Preleukemia. Berlin: Springer Verlag, 1979, pp. 24–34.Google Scholar
  56. 56.
    Bainton DF. Abnormal neutrophils in acute myelogenous leukemia: Identification of subpopulations based on analysis of azurophil and specific granules. Blood Cells 1:191–199, 1975-Google Scholar
  57. 57.
    Kobayasi T, Asboe-Hansen G Ruthenium red staining of ultrathin sections of human mast cell granules. J Microsc 93: 55–60, 1971.PubMedCrossRefGoogle Scholar
  58. 58.
    Parkin J, McKenna R. Brunning RD. Ultrastructural features of basophil and mast cell granulopoiesis in blastic phase Philadelphia chromosome-positive leukemia. J Natl Cancer Inst 65 535–546, 1980.PubMedGoogle Scholar
  59. 59.
    Parkin J, McKenna R, Brunning R. Philadelphia chromosome-positive blastic leukemia: Ultrastructural and ultracy- tochemical evidence of basophil and mast cell differentiation. Br J Haematol 52: 663–677, 1982.PubMedCrossRefGoogle Scholar
  60. 60.
    Parkin J, Abramson C, McKenna R, Arthur D, Kersey J, Heideman R, Brunning R. Acute leukemia associated with the t(4;l 1) chromosome rearrangement: Ultrastructural and immunologic characteristics. Blood 60: 1321–1331, 1982.PubMedGoogle Scholar
  61. 61.
    Freeman Al, Journey LJ. Ultrastrucrural studies on monocytic leukemia. Br J Haematol 20: 225–231, 1971.PubMedCrossRefGoogle Scholar
  62. 62.
    Glick AD, Horn RG. Identification of promonocytes and monocytoid precursors in acute leukemia of adults: Ultrastructural and cytochemical observations. Br J Haematol 26. 395–403, 1974.PubMedCrossRefGoogle Scholar
  63. Breton-Gorius J, Dreyfus B. Sultan C. Basch A. d’Oliveira JG. Identification of circulating micromegakaryocytes in a case of refractory anemia: An electron micro- scopic-cytochcmical study. Blood 40: 453–463, 1972.Google Scholar
  64. 64.
    Den Ottolander GJ, te Velde J, Brederoo P. Geraedts JPM, Sice PHT, Willemze R. Zwaan FE, Haak HL, Müller IIP, Bieber R. Megakaryoblastic leukemia (acute myelofibrosis): A report of three cases. Br J Haematol 42: 9–20. 1979CrossRefGoogle Scholar
  65. 65.
    Maldonado JF., Pintado T, Pierre RV. Dysplasia platelets and circulating megakaryocytes in chronic myeloproliferative disease: I. The platelets: Ultrastructure and peroxidase reaction. Blood 43: 797–809, 1974.PubMedGoogle Scholar
  66. 66.
    Maldonado JE. Dysplastic platelets and circulating megakaryocytes in chronic myeloproliferative disease II. Ultrastructure of circulating megakaryocytes. Blood 43:811–820, 1974.Google Scholar
  67. 67.
    Maldonado JE. Giant platelet granules in refractory anemia (preleukemia) and myelomonocytic leukemia: A cell marker? Blood Cells 1:129–135, 1975.Google Scholar
  68. 68.
    Linker H. The platelet ultrastructure in preleukemia. In: Schmalzl F, Hellriegel KP, eds. Preleukemia. Berlin: Springer Verlag. 1979, pp. 35–40.Google Scholar
  69. 69.
    Mitelman F, Brandt L, Nilsson PG Relation among occupational exposure to potential mutagenic/carcinogenic agents, clinical findings and bone marrow chromosomes in acute nonlymphocytic leukemia. Blood 52:1229–1237, 1978.Google Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston/The Hague/Dordrecht/Lancaster 1984

Authors and Affiliations

  • Robert W. McKenna
  • Janet L. Parkin
  • Richard D. Brunning

There are no affiliations available

Personalised recommendations