נויטרופניה כרונית

ד"ר ציצוביץ שלום רב. אני סובלת מגיל 17 מ persistent chronic neutropenia וכמות הליקוציטים שלי ביום טוב עומד על 3000 וזאת בעזרת זריקות של גראנוצייט פעמיים בשבוע. אני רוצה להתחיל טיפולי פוריות עקב בעייה שקיימת בחצוצרות, הטיפולים הם כל מה שכרוך בהפריית מבחנה. התייעצתי עם הרופא המטולוג שלי ואמר שלא צריכה להיות בעייה, אבל הוא שאנן מידי לטעמי. אני נורא חוששת ורציתי לשאול אותך האם על פי נסיונך יש סכנה לאם ולילד כשברקע סיפור כזה? האם הזריקות של הגרנוצייט יכולים לגרום מומים בעובר? אני כבר התייאשתי מלחפש חומר באינטרנט והפניות שלי למרכזים הארציים לייעוץ טרטולוגי העלו חרס. התשובות שלהם כלליות מידי ואמרו שאין מספיק מחקרים בנושא. אני נורא נורא מבקשת את עזרתך אולי אפילו שתפנה אותי לפורום עולמי ששם אוכל לקבל תשובות אולי מנשים אחרות במצבי שעברו טיפולים והריון. בהערכה רבה, האלמונית

התשובות אינן מתחמקות. אכן אין מחקרים בנושא זה (מסיבות ברורות) והמידע שקיים מתבסס על מקרים ספורדיים. חברות התרופות מציינות זאת במפורש לגבי התכשירים הרלבנטייים. ההתלבטות בנושא אינה חסרת הגיון, בעיקר לאור העובדה שבשליה יש הרבה קולטנים ל- G-CSF ואין לדעת מה השפעת התרופה על השליה. ראי: http://journals.endocrinology.org/joe/149/joe1490249.htm מאידך, יש דיווחים על נשים שעברו הריון תוך טיפול בתרופה זו במחלה שאת סובלת ממנה: ראי: http://depts.washington.edu/registry/Sum96.pdf יש במאמר טבלה עם פירוט של ההריונות ומצב היילודים. המסקנה היא שאם מצב האם מחייב את הטיפול הרי שיש לעשות זאת בתיאום בין האם והרופאים ותוך הבנה ברורה של המצב. וגם כאן: http://depts.washington.edu/registry/Fall96.pdf וכאן http://depts.washington.edu/registry/Fall99.pdf עוד מקורות: אתר בינלאומי בנושא זה: http://depts.washington.edu/registry ויש עוד המון מקורות לנושא: http://www.google.com/search?num=20&hl=en&lr=lang_en&ie=ISO-8859-1&newwindow=1&q=severe+chronic+neutropenia+support http://www.neutropenia.ca/about/treatment.html http://www.tthhivclinic.com/gcsf.htm http://www.bccancer.bc.ca/HPI/DrugDatabase/Appendices/Appendix4/FilgrastimPtInfo.htm http://www.emedicine.com/ped/topic1260.htm הנה ציטוט המסכם מעקב של חולים הסובלים מ- SCN ומטופלים ב- G-CFS כולל נשים בהריון: Am J Hematol 2003 Feb;72(2):82-93 Severe chronic neutropenia: Treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry. Dale DC, Cottle TE, Fier CJ, Bolyard AA, Bonilla MA, Boxer LA, Cham B, Freedman MH, Kannourakis G, Kinsey SE, Davis R, Scarlata D, Schwinzer B, Zeidler C, Welte K. University of Washington, Seattle, Washington. Severe chronic neutropenia (SCN) is defined as an absolute neutrophil (ANC) of less than 0.5 x 10(9)/L, lasting for months or years. Congenital, cyclic, and idiopathic neutropenia are principal categories of SCN. Since 1994, the Severe Chronic Neutropenia International Registry (SCNIR) has collected data to monitor the clinical course, treatments, and disease outcomes for SCN patients. This report summarizes data for 853 patients, almost all treated with daily or alternate-day recombinant human granulocyte colony-stimulating factor (G-CSF or Filgrastim). G-CSF treatment increased the ANC overall from 0.34 x 10(9)/L +/- 0.018 pre-treatment to 3.70 x 10(9)/L +/- 0.18 during the first year of treatment. For most patients, the responses were durable with patients remaining on the same dose of G-CSF for many years. Long-term hematological observations showed stable mean leukocyte and neutrophil counts and gradually increasing hemoglobin levels. Thrombocytopenia developed in 4% of patients. As of January 1, 2000, myelodysplasia (MDS) or acute myelogenous leukemia (AML) has occurred in 35 of 387 patients with congenital neutropenia with a cumulative risk of 13% after 8 years of G-CSF treatment. This event occurred without a predictable relationship to the duration or dose of G-CSF treatment. No patients with cyclic or idiopathic neutropenia developed MDS or AML. Other important adverse events included hepatomegaly, osteoporosis, vasculitis, glomerulonephritis, and deaths in 4 of 14 cases requiring splenectomy. Growth and development and the outcome of pregnancy appeared to be unaffected by G-CSF treatment. These data indicate that congenital, cyclic, and idiopathic neutropenia can be effectively treated with long-term G-CSF. The risk of leukemia, osteoporosis, other potentially adverse events, and pregnancy outcome need to be further evaluated with continuing long-term observations. Am. J. Hematol. 72:82-93, 2003. Copyright 2003 Wiley-Liss, Inc ************************************ Semin Hematol 1997 Oct;34(4):267-78 Related Articles, Links Severe chronic neutropenia: pathophysiology and therapy. Welte K, Boxer LA. Department of Pediatric Hematology and Oncology, Medical School Hannover, Germany. The development of recombinant-met human granulocyte-colony stimulating factor (r-metHuG-CSF) for clinical use has had a major influence on the treatment of many diseases. This impact has perhaps been greatest for treatment of severe chronic neutropenia (SCN) conditions for which there were no predictably effective treatment before the availability of these growth factors, particularly r-metHuG-CSF (Filgrastim, Amgen Inc, Thousand Oaks, CA; or Lenograstim, Rhone-Poulenc Rorer, Milan, Italy). Based on careful studies in many countries it is now known that more than 95% of these patients will respond promptly to r-metHuG-CSF treatment with normalization of the blood neutrophil levels and reduction in the occurrence of both major and minor consequences of their severe neutropenia. The availability of this treatment will undoubtedly lead to much additional research on the mechanisms governing neutrophil production and the basic mechanisms that can cause neutropenia among patients who have SCN. Among patients who have SCN those who are diagnosed to have severe congenital neutropenia (Kostmann's syndrome) or Shwachman-Diamond syndrome are at risk of developing myelodysplasia and/or acute myelogenous leukemia. The role of r-metHuG-CSF in facilitating the risk remains to be determined. Thus, it is important that long-term evaluation of the safety and efficacy of treatment of SCN and cooperation in research on these rare conditions proceed under the auspices of an international registry monitoring the clinical outcome of patients with severe congenital neutropenia ********************************************************** וזה ציטוט אחר, לא ברור כמה רלבנטי לך, אבל חשוב לקרוא: Blood, Vol. 96 No. 2 (July 15), 2000: pp. 429-436 Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy Melvin H. Freedman, Mary Ann Bonilla, Carol Fier, Audrey Anna Bolyard, Debra Scarlata, Laurence A. Boxer, Sherri Brown, Bonnie Cham, George Kannourakis, Sally E. Kinsey, Pier Georgio Mori, Tammy Cottle, Karl Welte, and David C. Dale From the Severe Chronic Neutropenia International Registry, University of Washington, and the University of Washington Department of Medicine, Seattle, WA; the University of Michigan Medical Center, Ann Arbor, MI; St Barnabas Medical Center, West Orange, NJ; the Clinical Safety Department, Amgen, Inc, Boulder, CO, and Thousand Oaks, CA; The Hospital for Sick Children and the University of Toronto Faculty of Medicine, Toronto, Ontario, Canada; the Manitoba Cancer Treatment and Research Foundation, Winnipeg, Manitoba, Canada; the Cancer Research Center, University of Ballarat; St James's University Hospital, Leeds, England; the Istituto Giannina Gaslini, Genova, Italy; and the Medizinische Hochschule, Hannover, Germany. Granulocyte colony-stimulating factor (G-CSF) has had a major impact on management of "severe chronic neutropenia," a collective term referring to congenital, idiopathic, or cyclic neutropenia. Almost all patients respond to G-CSF with increased neutrophils, reduced infections, and improved survival. Some responders with congenital neutropenia have developed myelodysplastic syndrome and acute myeloblastic leukemia (MDS/AML), which raises the question of the role of G-CSF in pathogenesis. The Severe Chronic Neutropenia International Registry (SCNIR), Seattle, WA, has data on 696 neutropenic patients, including 352 patients with congenital neutropenia, treated with G-CSF from 1987 to present. Treatment and patient demographic data were analyzed. The 352 congenital patients were observed for a mean of 6 years (range, 0.1-11 years) while being treated. Of these patients, 31 developed MDS/AML, for a crude rate of malignant transformation of nearly 9%. None of the 344 patients with idiopathic or cyclic neutropenia developed MDS/AML. Transformation was associated with acquired marrow cytogenetic clonal changes: 18 patients developed a partial or complete loss of chromosome 7, and 9 patients manifested abnormalities of chromosome 21 (usually trisomy 21). For each yearly treatment interval, the annual rate of MDS/AML development was less than 2%. No significant relationships between age at onset of MDS/AML and patient gender, G-CSF dose, or treatment duration were found (P > .15). In addition to the 31 patients who developed MDS/AML, the SCNIR also has data on 9 additional neutropenic patients whose bone marrow studies show cytogenetic clonal changes but the patients are without transformation to MDS/AML. Although our data does not support a cause-and-effect relationship between development of MDS/AML and G-CSF therapy or other patient demographics, we cannot exclude a direct contribution of G-CSF in the pathogenesis of MDS/AML. This issue is unclear because MDS/AML was not seen in cyclic or idiopathic neutropenia. Improved survival of congenital neutropenia patients receiving G-CSF therapy may allow time for the expression of the leukemic predisposition that characterizes the natural history of these disorders. However, other factors related to G-CSF may also be operative in the setting of congenital neutropenia לסיכום: איני חושב שהטיפול צריך להפריע לתהליך ההפריה, ולגבי הטיפול במהלך ההריון - צריך להבין שיש בכך סיכון מסויים ובלתי ידוע, אבל יש בזה גם הרבה סיכוי להצלחה.

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