What is the duration of remission after Bone Marrow Transplant (BMT) for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)?

Duration of Remission After BMT for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Patients who undergo allogeneic hematopoietic cell transplantation (HCT) in first complete remission for BPDCN can achieve long-term remission with median overall survival of 38.4 months, with some patients remaining disease-free beyond 5 years. 1

Remission Duration by Treatment Approach

Allogeneic HCT Outcomes

Allogeneic HCT has demonstrated the most promising results for sustained remission in BPDCN:

• First Complete Remission (CR1):

  • 5-year progression-free survival (PFS) and overall survival (OS) rates of 80% for patients transplanted in CR1 2
  • Median OS of 38.5 months with allogeneic HCT 1
  • 3-year OS of 74% when performed in first CR versus 0% when not in first CR 1

• Conditioning Regimens:

  • Total body irradiation (TBI) as conditioning backbone significantly improves outcomes 1
  • 2-year PFS of 95% for myeloablative conditioning with TBI versus 82% without TBI 1
  • No significant difference between myeloablative and reduced-intensity conditioning in some studies 1

Autologous HCT Outcomes

• 4-year OS rate of 82% when performed in first CR 1
• 4-year PFS rate of 73% 1
• However, contradictory data shows 1-year OS of only 11% in another study 1

Non-Transplant Approaches

Without HCT, remission durations are significantly shorter:

• Tagraxofusp (SL-401) first-line therapy: median OS of 15.8 months 1
• Chemotherapy alone: median OS of 7.1-12.3 months depending on regimen type 1
• Median duration of response with tagraxofusp: 5 months (range 1-201 months) 1

Factors Affecting Remission Duration

Several factors significantly impact the duration of remission after BMT:

1. Disease status at transplant: First CR is the most important predictor of long-term remission

   • 5-year OS/PFS of 80% in CR1 versus 0% in non-CR1 2

2. Age at diagnosis:

   • Median OS of 12.6 months in patients <65 years versus 7.1 months for those >65 years 1

3. Type of induction therapy before BMT:

   • ALL-type regimens (like hyper-CVAD) show higher CR rates (80%) 1, 3
   • Tagraxofusp shows 59% CR rate 3
   • Both can effectively bridge to transplant (49-51% of patients) 3

4. Transplant conditioning regimen:

   • TBI-based conditioning shows superior outcomes 1
   • Myeloablative conditioning with TBI: 95% 2-year PFS 1

Clinical Approach to Maximize Remission Duration

To achieve the longest possible remission:

1. Aim for complete remission before transplant

   • Use effective induction therapy (tagraxofusp or hyper-CVAD) 1, 3
   • Consider CNS prophylaxis as CNS relapses are common 3

2. Proceed to transplant while in first CR

   • This is the single most important factor for long-term remission 1, 2, 4
   • Even patients with initial skin-only disease should be considered for transplant 4

3. Select optimal transplant approach

   • Allogeneic HCT with TBI-based conditioning when possible 1
   • Consider autologous HCT in first CR if allogeneic not feasible 1

4. Monitor for relapse

   • For relapsed patients post-transplant, donor lymphocyte infusions may induce remission through graft-versus-leukemia effect 5

Pitfalls and Caveats

• Delayed transplant: Waiting until relapse dramatically reduces chances of long-term remission
• Inadequate induction: Failure to achieve CR before transplant significantly worsens outcomes
• CNS prophylaxis: Omitting CNS-directed therapy may lead to CNS relapse 3
• Comorbidities: Age and comorbidities may necessitate reduced-intensity conditioning, which may have lower efficacy without TBI 1
• Post-transplant complications: Monitor for GVHD and post-transplant lymphoproliferative disorders, especially with cord blood transplants 5

In summary, while BPDCN generally has a poor prognosis, allogeneic HCT performed in first complete remission offers the best chance for long-term remission, with many patients remaining disease-free beyond 5 years. The timing of transplant (in first CR) is more critical than the specific induction regimen used to achieve remission.