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304 <strong>Haematologica</strong> (ed. esp.), volumen 85, supl. 2, octubre 2000 Por lo general en el MM tanto la respuesta al tratamiento como la supervivencia son mejores cuando la RM es normal que cuando está alterada 13 . En conclusión, la RM de médula ósea permite realizar de forma no invasiva, un estudio aproximativo de la celularidad hemopoyética en las diversas situaciones hematológicas. Las posibles alteraciones de señal objetivadas, difusas o focales, constituyen un complemento y en ocasiones una alternativa a la biopsia medular, a la vez que a menudo son la pista inicial que conduce al diagnóstico acertado. Bibliografía 1. Kangarloo H, Dietrich RB, Taira RT et al. MR imaging of bone marrow in children. J Comput Assist Tomogr 1986; 10: 205-209. 2. Vogler JB, Murphy WA. Bone marrow imaging. Radiology 1988; 168: 679-693. 3. Steiner RM, Mitchell DG, Rao VM, Schweitzer ME. Magnetic resonance imaging of diffuse bone marrow disease. Radiol Clin North Am 1993; 31: 383-409. 4. Moulopoulos LA, Dimopoulos MA. Magnetic resonance imaging of the bone marrow in hematologic malignancies. Blood 1997; 90: 2127-2147. 5. McKinstry CS, Steiner RE, Young AT, Jones L, Swirsky D, Aber V. Bone marrow in leukemia an aplastic anemia: MR imaging before, during and after treatment. Radiology 1987; 162: 701-707. 6. Takagi S, Tanaka O, Miura Y. Magnetic resonance imaging of femoral marrow in patients with myelodysplastic syndromes or leukemia. Blood 1995; 86: 316-322. 7. Depaoli L, Davini O, Foggetti MD et al. Evaluation of bone marrow cellularity by magnetic resonance imaging in patients with myelodysplastic syndrome. Eur J Haematol 1992; 49: 105-107. 8. Jensen KE, Nielsen H, Thomsen C et al. In vivo measurements of the T1 relazation processes in the bone marrow in patients with myelodysplastic syndrome. Acta Radiol 1989; 30: 365-368. 9. Van de Berg BC, Michaux L, Scheiff JM et al. Sequential quantitative MR analysis of bone marrow: differences during treatment of lymphoid versus myeloid leukemia. Radiology 1996; 201: 519-523. 10. Silingardi V, Davolio-Marani S, Federico M et al. Bone marrow infiltration in hairy cell leukemia after interferon therapy detected by magnetic resonance imaging. Eur J Cancer Clin Oncol 1989; 23: 209-213. 11. Libshitz HI, Malthouse SR, Cunningham D, MacVicar AD, Husband JE. Multiple myeloma: appearance at MR imaging. Radiology 1992; 182: 833-837. 12. Moulopoulos LA, Varma DGK, Dimopoulos MA et al. Multiple myeloma: spinal MR imaging in patients with untreated newly diagnosed disease. Radiology 1992; 185: 833-840. 13. Moulopoulos LA, Dimopoulos MA, Simith TL et al. Prognostic significance of magnetic resonance imaging in patients with asymptomatic multiple myeloma. J Clin Oncol 1995; 13: 251-256. 14. Van de Berg BC, Michaux L, Lecouvet FE et al. Nonmyelomatous monoclonal gammopathy:correlation of bone marrow MR images with laboratory findings and spontaneous clinical outcome. Radiology 1997; 202: 247-251. 15. Kusumoto S, Jinnal I, Itoh K et al. Magnetic resonance imaging patterns in patients with multiple myeloma. Br J Haematol 1997; 99: 649-655. 16. Negendank WG, Al-Katib AM, Karnes C, Smith MR. Lymphomas: MR imaging contrast characteristics with clinical-pathologic correlations. Radiology 1990; 177: 209-216. 17. Lanir A, Aghai E, Simon JS, Lee RGL, Clouse ME. MR imaging in myelofibrosis. J Comput Assist Tomogr 1986; 10: 634-636. 18. Ricci C, Cova M, Kang YS et al. Normal age-related patterns of cellular and fatty bone marrow distribution in the axial skeleton: MR imaging study. Radiology 1990; 177: 83-88. 19. Schick F, Einsele H, Wei B, Jung WI, Lutz O, Claussen CD. Characterization of bone marrow after transplantation by means of magnetic resonance. Ann Hematol 1995; 70: 3-13. 20. Rozman C, Mercader JM, Rozman M, Aguilar JL. Resonancia magnética de la médula ósea vertebral: Análisis densitométrico. Med Clín (Barc) 1996; 106: 521-524. 21. Sanz Ll, Cervantes F, Mercader JM, Rozman M, Rozman C, Montserrat E. Afección oculta de la médula ósea en la enfermedad de Hodgkin: detección por resonancia magnética. Med Clín (Barc) 1996; 107: 143-145. 22. Rozman M, Mercader JM, Aguilar JLl, Montserrat E, Rozman C. Estimation of bone marrow cellularity by means of vertebral magnetic resonance. <strong>Haematologica</strong> 1997; 82: 166-170. 23. Sanz Ll, Bladé J, Olondo M et al. Contribución de la resonancia magnética al diagnóstico diferencial de un colapso vertebral en un paciente con mieloma múltiple. Sangre 1998; 43: 77-81. 24. Rozman M, Feliu E, Rozman C. Bone marrow biopsy in the management of Hodgkin’s disease: is it useful Hematology Review 1994; 8: 295-304. 25. O’Carroll DI, McKenna RW, Brunning RD. Bone marrow manifestations of Hodgkin’s disease. Biology, treatment, prognosos. Blood 1981; 57: 813-822. 26. Bartl R, Frich B, Burkhardt R, Huhn D, Pappenberger R. Assessment of bone marrow histology in Hodgkin’s disease: correlation with clinical factors. Br J Haematol 1982; 51: 345-360. 27. Shields AF, Porter BA, Churchley S, Olson DO, Appelbaum FR, Thomas ED. The detection of bone marrow involvement by lymphoma using magnetic resonance imaging. J Clin Oncol 1987; 5: 225-230. 28. Linden A, Zankovich R, Theissen P, Diehl V, Schicha H. Malignant lymphoma: bone marrow imaging versus biopsy. Radiology 1989; 173: 335-339. 29. Döhner H, Gückel F, Kanuf W et al. Magnetic resonance imaging of bone marrow in lymphoproliferative disorders: correlation with bone marrow biopsy. Br J Haematol 1989; 73: 12-17. 30. Rozman, C, Cervantes, F, Rozman, M, Mercader, JM, Montserrat, E. Magnetic resonance imaging in myelofibrosis and essential thrombocythaemia: contribution to differential diagnosis. Br J Haematol 1999; 104:574-580. 31. Guermazi A, Miaux Y, Chiras J. Imaging of spinal cord compression due to thoracic extramedullary haematopoiesis in myelofibrosis. Neuroradiology 1997; 39: 733-736. DIAGNOSTIC PROCEDURES FOR LYMPHOMA P.L. ZINZANI AND M. BENDANDI Institute of Haematology and Medical Oncology. “L. e A. Seragnoli”. University of Bologna. Bologna, Italy. Over the past twenty years the dramatic technical improvement of the diagnostic procedures used to monitor lymphomas from their onset through the longer lasting follow-ups probably accounts for the constant increase of the number of long-term survivals. As a matter of fact, the almost concomitant improvement of quality treatments for lymphoma has proved so far more emphasized than demonstrated 1 , whereas no doubts remain on the fact that greater diagnostic accuracy has been achieved and keeps being achieved, providing more and more reliable data during both the staging and monitoring phases. Another remarkable feature of this diagnostic progress is represented by the fact that it has been achieved somehow coupled to the effort of rendering all the procedures involved as little invasive as possible. Better definition has not meant worse quality of life for the patient undergoing the examinations, as opposed to what very often happens with respect to therapy, when “more” almost always means “more toxic” as well. Non-invasive procedures have got more and more precise, as invasive diagnostic tools have proven themselves sharper and less disturbing for the patients. The logical middle-term conclusion of this diagnostic revolution in the field of lymphoma is that, currently, the classical staging of both Hodgkin’s disease (HD) and non-Hodgkin’s lymphoma (NHL) needs to be integrated with novel procedures more and more often. Of the three definitely invasive staging procedures historically associated with HD, only bipedal lymphangiography is still surviving, while both laparotomy with splenectomy and laparoscopy with multiple hepatic and splenic biopsies are generally regarded as only exceptionally indispensable. Similarly,
XLII Reunión Nacional de la AEHH y XVI Congreso de la SETH. Foros de debate 305 as a common finding in both HD and NHL, more and more frequently a computed tomography (CT) scan tends to replace the combination of chest radiogram and abdomen ultrasonography (US). Among non-invasive procedures both gallium-67- citrate single photon emission ( 67 GaSPECT) 2,3 and positron emission tomography (PET) 4,5 have come into their own, with important consequences on the management of lymphoma patients, whereas two invasive procedures proven very compelling are core-needle biopsy of the mediastinal 6 and abdominal 7 .lymph nodes. Here we are going to summarize our personal and institutional experience with respect to all the above mentioned novel staging and monitoring procedures. Gallium-67-citrate single photon emission Residual masses in the mediastinum following lymphoma therapy are as common as troubling for both patients and physicians, to such an extent that, when in doubt concerning the real nature of the residue, both of them generally feel obliged to think that, therapy-wise, “more is better” or at least “safer”. CT scan and nuclear magnetic resonance (NMR) often prove not adequate in order to discriminate beyond a reasonable doubt between active tumour and fibrotic tissue and the use of the former, definitely more widespread in Italy than the latter, often does not allow to perfectly monitor during the follow-up patients who were diagnosed with a bulky lesion in the mediastinum. This is the reason for we started in 1992 a study 8 associating and comparing CT scan and 67 GaSPECT in patients with either HD or aggressive NHL presenting mediastinal involvement (64 % with bulky mass). The study design was essentially based on this double evaluation being performed at the end of standard combined modality treatments (chemoand radio-therapy) all patients had undergone. Once this specific response analysis was completed, each and every patient was allotted to one of the following four categories: CT negative/ 67 GaS- PECT positive, CT negative/ 67 GaSPECT negative, CT positive/ 67 GaSPECT positive and CT positive/ 67 GaS- PECT negative. All the three patients who resulted CT negative and 67 GaSPECT positive at the time of restaging following the completion of both chemo and radio-therapy relapsed within 15 months. Among the 18 patients who were CT negative and 67 GaSPECT negative, seventeen have maintained their clinical complete response (CCR), whereas one patient relapsed 18 months later with lung and neck localizations of HD. As many as ten of the 13 (77 %) patients being CT positive and 67 GaSPECT positive relapsed, in nine cases within 5 months and in one case after 10 months. Finally, only 5 of 41 (12 %) patients who ended up as CT positive and 67 GaSPECT negative relapsed. However, the most astounding difference emerged from the comparison in terms of 4-year actuarial relapse-free survival (RFS) rate between CT positive/ 67 GaSPECT negative and CT positive/ 67 GaSPECT positive patients (90 % vs 23 %; p < 0.000000). We conclude that 67 GaSPECT should become somehow mandatory among the restaging procedures for lymphoma, at least with respect to patients with mediastinal involvement at diagnosis and CT scan positivity at the end of the treatment. Then, in case of 67 GaSPECT positivity, a local biopsy might be warranted. Positron emission tomography If the 67 GaSPECT has proven extremely useful in order to discriminate between fibrosis and neoplasia in the residual masses of the mediastinum, the same cannot be said when the same dilemma refers to residual masses in the abdomen. As a matter of fact, mainly due to hepatic uptake and bowel excretion of the radionuclide, 67 GaSPECT yields too many false positives below the diaphragm to be somehow considered as reliable as it is above. Inasmuch as a number of reports had recently shown a possible role for fluorine-18 fluorodeoxyglucose PET in the context of lymphoma imaging, we started our own study on it in 1996 9 and over the next two years enrolled 44 patients with either HD or aggressive NHL, in both cases with at least an abdominal localization larger than 5 centimetres (41 % of the patients had a bulky mass). All patients received the appropriate chemo- and/or radio-therapy and their restaging included PET 1 month after completion of chemotherapy or two months after the end of radiotherapy, when given. Once the response analysis was completed, each and every patient was allotted to one of the following three categories: CT negative/PET negative, CT positive/PET positive and CT positive/PET negative. No patients were ever CT negative and PET positive at the same time. All 7 patients who were negative with respect to both procedures at the completion of their therapy have maintained their CCR. On the contrary, no patients with double positivity were able to avoid relapsing, in 11 cases within 8 months. Of the 24 patients who were CT positive and PET negative, all but one have also maintained their CCR, with a current median follow-up of 18 months. Once again, an extremely significative data is represented by the difference in terms of 2-year actuarial RFS between CT positive patients who were respectively PET negative or positive (95 % vs 0 %; p < 0.000000). Similarly to what concluded with respect to the 67 GaSPECT in lymphoma imaging above the diaphragm, we think that PET should be used mandatorily at the time of lymphoma restaging in all of the patients diagnosed with abdominal masses that are still CT positive at the end of treatment.
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