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  • Allogeneic bone marrow transplantation  (1)
  • Ph1+-ALL  (1)
  • 1
    ISSN: 1432-0584
    Keywords: Chronic myelogenous leukemia ; Allogeneic bone marrow transplantation ; Minimal residual disease ; BCR/ABL mRNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A modified two-step polymerase chain reaction (PCR) was used for the amplification of BCR/ABL mRNA in 16 patients with Philadelphia chromosomepositive (Ph+) chronic myelogenous leukemia (CML) following allogeneic bone marrow transplantation (BMT). At different intervals after BMT, patient cells were assessed for the presence of BCR/ABL mRNA by two subsequent rounds of PCR amplification; this procedure increased the sensitivity for the detection of one Ph+ cell in 104–5 to one cell in 105–6. Eight of 16 patients were negative by two-step PCR 1–39 months after BMT, suggesting an elimination of Ph-positive cells or a decrease below the threshold of detection. Although five patients showed negative results by the one-step PCR only, they were tested positive when nested primers were used, indicating a substantial decrease in the amount of BCR/ABL target mRNA compared with earlier pre- or post-transplant analyses. One patient who was still PCR positive 27 months after BMT became negative 12 months later. Persistence of BCR/ABL mRNA-expressing cells correlated with subsequent clinical relapse only when the transplantation was performed during blast crisis. All patients who underwent transplantation in chronic phase, including those with BCR rearrangement by PCR, are in clinical and hematological remission between 24 and 95 months after BMT. We conclude that aggressive chemotherapy combined with total body irradiation is unable to completely eradicate the malignant clone in all CML patients, and it might be speculated that other mechanisms (e.g., graft versus host reaction [GVHD] or graft versus leukemia effect [GVL]) may effectively eliminate residual leukemic cells.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Ph1+-ALL ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Between 1983 and 1991 the Philadelphia chromosome (Ph1) was found in bone marrow and/or peripheral blood cells of 25 adult patients with acute lymphoblastic leukemia (ALL). The Ph1 as sole anomaly was seen in 13 patients, while six patients had additional structural and another six structural and numerical aberrations. Most patients (23/25) received combination chemotherapy according to the BMFT protocols 1/81, 2/84, 3/87, and 4/89. For 25 evaluable patients two early deaths, two treatment failures, two partial remissions (PR), and 19 complete remissions (CR) after phase 1 or 2 of the induction regimen were recorded. Two of these 19 patients who achieved CR are presently disease free, whereas 17 have relapsed after a median duration of remission of 9 months. Actuarial median survival for all patients was 13 months. The probability of continuous complete remission (CCR) after 39 months, as well as that of survival after 40 months, is only 6%. Our results confirm that the presence of the Ph1 is associated with a poor prognosis in adult-ALL patients. Therefore, whenever first CR is obtained and an HLA-identical donor is available, allogeneic bone marrow transplantation (BMT) should be performed at once, the more so, since transplantation in second CR seems to offer no cure. Future studies will have to show whether an intensified cytotoxic therapy can improve the prognosis of Ph1+-ALL.
    Type of Medium: Electronic Resource
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