Other Reinduction and Salvage Chemotherapy

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See Table 15-18.

Autologous Stem Cell Transplantation

Preparative Regimes

A variety of high-dose chemotherapy regimens, including cyclophosphamide, etoposide, and BCNU (CBV) (Table 16-13 in Chapter 16) and BCNU, etoposide, Ara-C, and melphalan (BEAM) (Table 16-14 in Chapter 16), are being utilized as preparative regimens for stem cell transplantation.

Table 15-20. Regimen of Vinorelbine (VRB) and Gemcitabine (GEM) in Relapsed or Refractory Hodgkin Disease

VRB 25 mg/m2/day Days 1 and 8

GEM 1000 mg/m2/day Days 1 and 8

G-CSF 5 ^g/kg/day starting on day 9 for a minimum of 7 days and until the ANC

>1500/mm3 for 3 days or the ANC >10,000/mm3.

• Two cycles—second cycle is administered 21-28 days later.

• Evaluation: If CR, peripheral stem cell harvest should be carried out after 2 cycles of VRB/GEM. This should be followed by HSCT preparatory regimen (Chapter 25) and peripheral stem cell transplantation.

• Evaluation: If stable disease is attained and/or PR, peripheral stem cell harvest should be carried out followed by two more cycles of VRB/GEM, HSCT preparatory regimen (cyclophosphamide, etoposide, and BCNU-CBV [Table 16-13] or BCNU, etoposide, Ara-C, melphalan-BEAM [Table 16-14]), and peripheral stem cell transplantation.

Indications

• Relapse within 1 year of completion of conventional treatment (except stage I or IIA where only radiotherapy has been employed, in which case the patient can be treated with chemotherapy)

• Patients refractory to initial treatment who do not achieve complete remission.

For these patients, autologous bone marrow transplantation (AuBMT) or autologous peripheral stem cell rescue may be utilized after two or three cycles of conventional chemotherapy.

Post-Stem Cell Transplantation Management

There seems to be a beneficial role of immunotherapy following stem cell transplantation. Immune modulation with interferon y (IFN-y) and IL-2 after autologous stem cell rescue has been demonstrated to reduce the rate of relapse and to improve survival. Currently, COG is conducting a study that incorporates immunotherapy with cyclosporine, IFN-y, and IL-2 during recovery after autologous stem cell rescue.

Prognosis

The early transplant-related mortality is 10% and the predominant reason for failure in patients who undergo salvage therapy is relapse.

Experience in children is limited. However, a report from the European Bone Marrow Transplant Group showed that 81 children with HD who underwent AuBMT had a long-term (>5 years) disease-free survival rate of 40%. A 1999 report from the Autologous Blood and Bone Marrow Registry (ABMTR) showed that 50% of patients who failed to achieve complete remission after one or more conventional therapy regimens achieved complete remission after autotransplantation.

Molecular Targeted Therapies

Studies of single-cell DNA amplification have documented the importance of signaling through NF-kB transcription factor both in the proliferation of Hodgkin and Reed-Sternberg (H/RS) cells and in suppression of apoptosis. Inhibition of proteo-some and NF-kB in particular is an attractive biologic strategy in the therapy of HD. The focus of future targeted studies in HD will incorporate novel agents (chemother-apeutic and biologic agents) and therapeutic strategies that perturb the NF-kB pathway.

PS-341 is a highly selective inhibitor of NF-kB activation, as a result of induction of apoptosis. Strategies for incorporation of P-341 with effective therapeutic regimens for patients with relapsed/refractory pediatric HD are under way.

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