Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed or Refractory High-Risk NBL.

This is an interventional treatment trial for Neuroblastoma focused on measuring recurrent or refractory neuroblastoma Read More

DISEASE CHARACTERISTICS:

• Diagnosis of high-risk neuroblastoma, meeting one of the following criteria:

  • Refractory disease, defined as no response, mixed response, or progressive disease after completion of induction therapy administered according to clinical trials COG-A3973 or COG-ANBL0532 (or other similar high-intensity induction regimen)
  • Relapsed following high-dose chemoradiotherapy including autologous stem cell transplantation

• Achieved a complete remission (CR), very good partial remission (VGPR), or partial remission (PR) after ≤ 2 different salvage regimens, as defined by the following:

  • In CR after treatment with some form of salvage therapy (e.g., ¹³¹I-MIBG, antibody-based therapy, or any other COG or NANT salvage-therapy regimen)

  • In VGPR or PR after salvage therapy

    • No more than 3 sites of skeletal disease as determined by an ¹²³I-MIBG scan (for regional involvement of the skeleton [e.g., pelvis, spine], the tumor involvement should be < 25% of the site)
    • Bone marrow involvement (< 25% neuroblasts) by morphologic exam within the past 2 weeks
    • Patients with soft tissue disease are eligible provided they exhibit either a VGPR or PR in the primary soft tissue mass and in any sites of metastatic soft tissue disease

• Disease status meeting one of the following criteria:

  • Minimal residual disease
  • Disease considered responsive to a salvage regimen
  • Stable disease
• No rapidly progressive disease

• Donors must meet one of the following criteria:

  • Matched, related donor (6/6 or 5/6) (bone marrow donor allowed)
  • HLA-matched unrelated donor (10/10 match on high-resolution [HR] typing of HLA-A, B, C, DRB1, and DQB1)
  • One allele- or antigen-mismatched unrelated donor (9/10 match on HR typing), mismatched at HLA-C only
  • One allele- or antigen-mismatched unrelated donor (9/10 match on HR typing), mismatched at HLA-A, B, DRB1, or DQB1 (only when HLA-C mismatch is not available)

PATIENT CHARACTERISTICS:

• Karnofsky/Lansky performance status 60-100%
• ANC > 500/mm^3
• Creatinine clearance or radioisotope GFR ≥ 60 mL/min
• Total bilirubin < 3.0 mg/dL
• AST or ALT < 5 times upper limit of normal
• Shortening fraction ≥ 25% by ECHO OR ejection fraction > 30% by MUGA
• FEV_1 and DLCO ≥ 30% OR normal chest x-ray, pulse oximetry, and venous blood gas
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No active or recent (within the past 30 days) fungal infection
• No proven or suspected sepsis, pneumonia, or meningitis unless appropriate therapeutic measures have been initiated to control the infection and systemic signs are no longer life-threatening
• No requirement for oxygen or ventilator support

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior tandem autologous stem cell transplantations (according to clinical trial COG-ANBL0532) allowed
• No prior allogeneic hematopoietic stem cell transplantation
• More than 2 months since prior autologous stem cell transplantation, myeloablative therapy, total-body irradiation, whole abdominal radiotherapy, or therapeutic ¹³¹I-MIBG
• More than 3 weeks since prior chemotherapy, immunotherapy (including anti-GD2 regimen), or biologic response modifiers and recovered
• More than 2 weeks since prior local radiotherapy to the sites of metastatic disease