A 45-year-old man with relapsed classical Hodgkin lymphoma (relapse 18 months after completing ABVD) is referred for salvage therapy. Which chemotherapy regimen is the drug of choice for salvage treatment?

Question

Accepted Answer

C. ESHAP (etoposide, sargamostim, cytarabine, cisplatin). ## Salvage Chemotherapy for Relapsed Hodgkin Lymphoma

**Key Point:** ESHAP (or other platinum-based salvage regimens like DHAP, ICE) is the standard salvage regimen for relapsed/refractory classical Hodgkin lymphoma. These regimens are designed to achieve chemosensitivity and allow subsequent stem cell transplantation (SCT).

### Salvage Regimen Strategy

**High-Yield:** The goal of salvage therapy is NOT cure with chemotherapy alone, but rather:
1. Achieve chemosensitivity (partial or complete response)
2. Mobilize and collect peripheral blood stem cells
3. Proceed to autologous SCT (ASCT), which offers 40–50% long-term survival in chemosensitive relapsed disease

### ESHAP Regimen Composition

| Drug | Dose | Mechanism | Role |
|------|------|-----------|------|
| Etoposide | 40 mg/m²/day × 4 | Topoisomerase II inhibitor | Backbone |
| Sargamostim (GM-CSF) | 250 μg/m²/day | Haematopoietic growth factor | Stem cell mobilization |
| Cytarabine (Ara-C) | 2000 mg/m²/day × 4 | Antimetabolite | Synergistic |
| Cisplatin | 25 mg/m²/day × 4 | Platinum alkylator | Broad-spectrum activity |

**Mnemonic:** **ESHAP** = **E**toposide, **S**argamostim, **H**igh-dose **A**ra-C, **P**latin (cisplatin)

### Why ABVD Rechallenge Fails

- **Cross-resistance:** Relapse within 12 months of ABVD indicates chemoresistant disease
- **Mechanism:** Tumour cells have developed resistance to ABVD components (doxorubicin, bleomycin, vinblastine, dacarbazine)
- **Outcome:** Repeating ABVD results in <10% response rate
- **Guideline:** ABVD rechallenge is only considered if relapse occurs >12 months after completion (late relapse, chemosensitive disease)

**Clinical Pearl:** This patient relapsed at 18 months — borderline timing. However, the standard approach is to use platinum-based salvage (ESHAP, DHAP, or ICE) followed by ASCT, as this offers superior long-term survival compared to ABVD rechallenge alone.

### Alternative Salvage Regimens

- **DHAP:** Dexamethasone, high-dose cytarabine, cisplatin (similar efficacy to ESHAP)
- **ICE:** Ifosfamide, carboplatin, etoposide (alternative platinum regimen)
- **Modern approach:** Checkpoint inhibitors (nivolumab, pembrolizumab) are increasingly used in relapsed/refractory disease, often as bridge to SCT

**Warning:** Do not confuse salvage therapy with primary therapy. ESHAP is NOT first-line (that is ABVD) but is the standard salvage approach.

Answer

A. Vinblastine monotherapy

Answer

B. ABVD rechallenge (repeat the same regimen)

Answer

D. Chlorambucil and prednisone

A 45-year-old man with relapsed classical Hodgkin lymphoma (relapse 18 months after completing ABVD) is referred for salvage therapy. Which chemotherapy regimen is the drug of choice for salvage treatment?

Explanation

Salvage Chemotherapy for Relapsed Hodgkin Lymphoma

Salvage Regimen Strategy

ESHAP Regimen Composition

Why ABVD Rechallenge Fails

Alternative Salvage Regimens

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Drug	Dose	Mechanism	Role
Etoposide	40 mg/m²/day × 4	Topoisomerase II inhibitor	Backbone
Sargamostim (GM-CSF)	250 μg/m²/day	Haematopoietic growth factor	Stem cell mobilization
Cytarabine (Ara-C)	2000 mg/m²/day × 4	Antimetabolite	Synergistic
Cisplatin	25 mg/m²/day × 4	Platinum alkylator	Broad-spectrum activity