Significance of the levels of bone marrow lymphoid infiltrate in chronic lymphocytic leukemia patients with nodular partial remission

Abstract

Patients with chronic lymphocytic leukemia (CLL) are considered in nodular partial remission (nPR) when they are in remission but bone marrow biopsies show rare nodules. The significance of the level of residual disease in nPR is not known. We studied 91 previously untreated CLL patients who were treated with fludarabine alone, fludarabine with prednisone, or fludarabine with cyclophosphamide and achieved nPR at the end of six courses. We compared bone marrow lymphoid infiltration before therapy and at the end of three and six courses of therapy as evaluated by a pathologist in retrospective fashion with that of the routine evaluation at the time of performing bone marrow biopsy. We then compared these results with those obtained by computer-aided histomorphometry in 28 patients in nPR. There was significant correlation (P Ͻ 0.05) between pathologists as well as between pathologists and histomorphometry. Upon correlation with clinical characteristics, there was significant correlation (P Ͻ 0.01) between marrow involvement before therapy and white blood cell counts (WBC), hemoglobin (Hgb), absolute lymphocyte counts, and ␤2-microglobulin (␤2-M) but none of these parameters correlated with the lymphoid infiltrate at the end of three or six courses of therapy. More importantly, lymphoid infiltration after three and six courses did not correlate with time to progression (TTP) or overall survival (OS). However, patients with Ͼ70% marrow involvement before therapy had a significantly shorter TTP (P = 0.02). All 91 patients showed similar results. However, we found reverse correlation between marrow lymphoid infiltrate at the end of three courses and OS (P = 0.01). Leukemia (2002) 16, 632-635.

Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute–Working Group 1996 guidelines

“…55,56 These nodules should be recorded as "nodular PR." Moreover, immunohistochemistry should be performed to define whether these nodules are composed primarily of T cells or lymphocytes other than CLL cells or of CLL cells.…”

Autologous stem cell transplantation as a first-line treatment strategy for chronic lymphocytic leukemia: a multicenter, randomized, controlled trial from the SFGM-TC and GFLLC

“…14,35 However, because of the lack of BM biopsies, our CR rate included nodular PRs and is not really comparable to the rates obtained in other studies, although the presence of residual nodules in BM (defining nodular PR) after the completion of therapy was not found to be correlated with time to progression or OS in a study by Oudat et al of patients treated with fludarabine with or without cyclophosphamide. 36 Furthermore, in our study, the median level of lymphocyte infiltration was 10%-11% after treatment completion, which is far below the 30% threshold recommended for CR in the 1996 guidelines. 24 MRD negativity has been considered an important goal in CLL.…”

Assessment of expression of selected Bcl-2 family proteins in lymphoid infiltration in patients with B-cell chronic lymphocytic leukaemia treated with nucleoside analogues.

“…This suggests that lymphoid cells with disturbed mechanism of apoptosis and excessive Bcl-2 expression were still present. The nPR is often observed in patients with CLL, which often suggests difficulties in achieving total remission of the disease regardless of administered treatment [11]. Nevertheless, purine nucleoside analogues treatment seems to bear significance.…”

“…In our studies intensity of immunohistochemical reaction was strong (+++) or moderate (++), which supports the possibility of performing tests on expression of Bcl-2 family proteins in trephine biopsy specimens of bone marrow. Bone marrow examination through TB with the help of immunohistochemical methods and image analysis supports its usefulness in prognosis of the course of the disease, assessment of efficacy of the administered treatment and MRD detection [11,12,18].…”

“…However, it is a useful diagnostic procedure in monitoring the course of the disease, its prognosis and assessment of MRD (minimal residual disease), i.a. nodular partial remission (nPR) in bone marrow [10][11][12]. In B-CLL leukaemic cells may infiltrate bone marrow in a diffuse, nodular, interstitial and mixed (nodular/interstitial) pattern.…”