Do Patients With Primary Refractory Disease Have A Suboptimal Outcome With Asct

While response to SC is the major selection criteria to proceed to ASCT, other prognostic factors also predict for long-term FFTF in patients with relapsed and refractory HL. Some groups have suggested that patients with primary refractory disease do less well than those patients who achieve an initial remission to front-line therapy. There are conflicting registry data in this regard.

The North American Autologous Blood and Bone Marrow Transplant Registry (ABMTR) reported on a series of 122 primary refractory patients having 3-year progression-free survival (PFS) and OS rates of 38 and 50%, respectively, using a variety of HDT regimens. Although chemosensitivity status was unknown in less than one-third of patients, it was concluded that only B symptoms at diagnosis and a poor performance status at the time of ASCT predicted for a poor outcome.

The Groupe d'Etudes des Lymphoma de l'Adulte (GELA) reported on a group of primary refractory patients defined as progression of disease on therapy, less than 50% response to front-line therapy, or persistent bone marrow involvement after four cycles of initial chemotherapy. These patients had poor outcomes with HDT and ASCT, with 5-year freedom from second failure of 23%, even though most patients (62%) had chemosensitive disease to SC.

The GHSG evaluated 206 patients with primary refractory disease defined as progression of disease on front-line therapy, or biopsy confirmation of active disease within 90 days posttherapy. While only 70 of these 206 patients actually received HDT and ASCT, the authors concluded that HDT was no better than standard chemoradiotherapy when the data were analyzed by intent to treat.21-24

An underlying problem with these published refractory disease series is the lack of a uniform definition of this entity. Definitions range from progression of disease on upfront therapy to a partial response 3 months posttreatment. Moreover, the inclusion of patients with unconfirmed pathology may result in treatment of patients with aggressive NHL, with a nonmalignant disorder (infection, or sarcoid-like reactions), or with residual radiologic abnormalities but no active HL with an HDT program. These non-HL entities are often strongly positive on gallium or positron emission tomography imaging, thereby making histologic confirmation even more imperative.25-28

We recently reported our data in primary refractory HL, which has longer median follow-up than any of the other reported series. This report is distinguished by a repeat biopsy confirming active HL in all patients. Among the 91 patients with primary refractory HL identified for this analysis, eight (9%) were found to have diffuse large B-cell lymphoma on the repeat biopsy. In these cases, the initial diagnosis of HL was confirmed by pathology review. The presence of an aggressive NHL has both prognostic significance and affects the choice of second-line therapy; for example, the use of anti-CD20-based therapy in patients with aggressive NHL may have a critical role (i.e., rituximab or high-dose radiolabeled anti-B1).29 With a median follow-up of

Figure 75.1 Overall survival of transplanted patients with relapsed or primary refractory disease

10 years, results at many centers including data at memorial Sloar Kettering Cancer center indicate that HDT/ASCT should be considered as standard treatment for patients with primary refractory HL if chemosensi-tive disease to SC is established. This is summarized in Table 75.1.30-34 We found no difference in FFTF for patients with chemosensitive primary refractory versus chemosensitive relapsed disease35 (Figure 75.1).

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