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LAST MONTH’S CLINICAL CHALLENGE

 

A 57-year-old man presented with axillary adenopathy. Biopsy of the axillary lymph node revealed mantle cell lymphoma with a diffuse pattern. The malignant cells were CD10-, CD19+, CD20+ and CD5+. PET-CT scan demonstrated bilateral axillary adenopathy, splenomegaly and bulky retroperitoneal adenopathy. FDG uptake was abnormal in all sites. Bone marrow biopsy revealed 20% involvement with lymphoma. Cytogenetic analysis showed the t(11;14) karyotype and PCR confirmed the presence of bcl-1. CBC was normal but LDH was elevated. The patient was staged as IVA. He received 6 cycles of R-HyperCVAD and obtained a CR. Bone marrow biopsy shows no evidence of disease by morphology and PCR. He has an HLA-matched sibling. What’s your recommended therapy?


YOUR RESPONSES

 
  • Autologous HCT – 27% 
  • Allogeneic myeloablative HCT – 9%
  • Reduced intensity allogeneic HCT – 35%
  • Radioimmunoconjugate – 4%
  • Rituximab maintenance – 10%
  • Observation – 15%
       

 

Commentary Provided by Ginna G. Laport, MD

Stanford University Medical Center

 

As seen in this case, the typical clinical course of mantle cell lymphoma is characterized by a high response rate to initial therapy. However, progression within 2 years or less tends to be the rule. If this patient was seen at our center, we would recommend consolidative therapy with reduced intensity conditioning (RIC) HCT since a matched related donor has been identified. The existence of a graft vs lymphoma effect is supported by reduced relapse rates after allografts in comparison to conventional chemotherapy and autografts. Additionally, RIC allografts have conferred responses in patients with relapsed/refractory disease including after a failed autograft1,2. If this patient did not have a MRD, my second choice would be autologous HCT as outcomes appear improved compared to conventional treatment3.

 

I would not recommend a myeloablative allograft in light of this patient’s age and the associated prohibitive nonrelapse mortality. The feasibility of radioimmunoconjugates has been reported in this setting4 and we are awaiting the results of the ECOG trial with which a single dose of Zevalin was administered after four cycles of R-CHOP as frontline therapy. Rituximab maintenance therapy after induction has been shown to prolong PFS but is associated with myelosuppression5. And finally, observation can be offered since no existing therapies have shown an unequivocal survival benefit compared to observation in a large, randomized trial. It should be acknowledged that this patient is probably not cured but would have several options once he relapses.

 

As confirmed by this poll, there is no uniform agreement and subsequent treatment decisions should be ultimately determined by the availability of specific clinical trials as well as patient and physician consideration of the risk/benefit ratio of current options.  The widespread distribution of votes here reminds us that an unequivocally superior therapy currently does not exist for mantle cell lymphoma in first remission.

 

1.       Armitage JO. Allotransplant for mantle cell lymphoma. Ann Oncol 2002;13(suppl 2):9a

2.       Khouri IF, et al. Nonablative allogeneic stem cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol 2003;21:4407

3.       Gianni AM, et al. Long-term remssion in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting. Blood 2003;102:749

4.       Zelentz A, et al.  Sequential rituximab with tositumomab/I131 followed by CHOP chemotherapy is a safe and highly effective regimen. Ann Oncol 2005;16(suppl5):54 (abstr 64)

5.       Kahl B, et al.  Maintenance rituximab following induction chemoimmunotherapy may prolong progression-free survival in mantle cell lymphoma: a pilot study from the  Wisconsin Oncology Network Study.  Ann Oncol 2006;17:1418