Treatment of NLPHL

To the editor:

The article on nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) by Drs Advani and Hoppe in Blood provides an excellent overview of this uncommon disease. However, their characterization of the outcome data available in the literature as supportive of continued use of radiation alone as the optimal treatment is somewhat incomplete and deserves careful re-examination.

It is important to remember that the large majority (∼80%) of patients with NLPHL present with stage I or II disease. Thus, the most relevant clinical evidence appropriately focuses on stage I and II disease. Additionally, the clinical course of NLPHL is indolent, and late relapses are regularly encountered, at least after radiation alone. For this reason, outcomes at ≥10 years from diagnosis are the most relevant.

As evidence of the effectiveness of radiation alone for limited stage NLPHL, Advani and Hoppe cite the pooled German Hodgkin Study Group data from the HD4 through HD12 studies,¹  claiming that the freedom from treatment failure (FFTF) was 93% after radiation alone. It is true that the 50-month FFTF was 93%, but it is more relevant that the 10-year FFTF was ∼75% and even more important that about one-half of the patients were treated with combined chemotherapy and radiation. Results for radiation alone are not provided in this paper.

My group at the British Columbia Cancer Agency recommends an alternative approach to NLPHL based on our observation that when one manages limited stage NLPHL using the same approach as for classical HL, results appear much improved compared with radiation alone.²  Using this approach for the 56 patients managed at our center over the last 20 years, we found a 10-year FFTF estimate of 98%. Readers might want to put the results cited by Advani and Hoppe into context using a level playing field. Table 1 shows the 10-year FFTF results for patients with limited stage NLPHL using the best estimate one can make based on the data published in each paper and, for the combined modality evidence, only includes series using chemotherapy equivalent to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). I omitted 1 paper because only about one-quarter of the 42 patients actually received combined modality treatment with ≥2 cycles of ABVD.³ 

Table 1 shows that, with radiation alone, the rate of treatment failure is ≥2 to 3 times greater than with combined modality treatment using brief ABVD, typically 2 cycles, followed by minimal field radiation, typically involved field. This reduction in treatment failure comes at a very modest price because 2 cycles of ABVD have virtually no long-term toxicity and with a major gain because reduction in the radiation field to minimal size reduces the risk of late toxicity.

The continued use of radiation alone for NLPHL is an accident of history and not the result of an evidence-based comparison. Clinicians should consider treating limited stage NLPHL the same as classical HL, especially given the available evidence that doing so appears to produce superior treatment outcomes.