Combination Chemotherapy Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or High-Risk Primary Refractory Hodgkin Lymphoma

OUTLINE: Patients are stratified according to response to prior therapy and risk factors
(those with presence of all 3 risk factors and failed primary therapy or primary progressive
disease vs. patients who relapse more than 100 days after an autologous stem cell
transplant).

- Salvage chemotherapy (IGV or MOPP): Patients who have previously received
mechlorethamine hydrochloride receive IGV; patients who have previously received a
gemcitabine-based regimen receive MOPP.

- IGV (ifosfamide, gemcitabine hydrochloride, and vinorelbine ditartrate): Patients
receive IGV combination chemotherapy comprising ifosfamide IV on days 1-4,
gemcitabine hydrochloride IV on days 1 and 4, and vinorelbine ditartrate IV on day
1. Treatment repeats every 2-3 weeks for 2-3 courses in the absence of disease
progression or unacceptable toxicity.

- MOPP (mechlorethamine hydrochloride, vincristine, procarbazine hydrochloride, and
prednisone): Patients receive MOPP combination chemotherapy comprising
mechlorethamine hydrochloride IV on days 1 and 8, vincristine IV on days 1 and 8,
oral procarbazine hydrochloride on days 1-14, and oral prednisone on days 1-14.
Treatment repeats every 4 weeks for at least 2 courses in the absence of disease
progression or unacceptable toxicity.

Patients with no progression of disease after salvage chemotherapy (at allograft work-up)
proceed to allogeneic hematopoietic stem cell transplantation [AHSCT]* within 60 days after
completion of salvage chemotherapy.

NOTE: *Patients with a nodal mass > 5 cm that has not ben previously irradiated and in the
absence of extranodal disease may undergo involved-field radiotherapy twice daily for 2
weeks, prior to AHSCT.

- AHSCT with reduced-intensity or non-myeloablative conditioning: Patients achieving
partial response or stable disease after salvage therapy receive fludarabine phosphate
IV over 30 minutes on days -6 to -2; melphalan IV over 15 minutes on days -6 and -5; and
undergo AHSCT on day 0 (reduced-intensity conditioning). Patients achieving complete
response after salvage therapy receive fludarabine phosphate IV over 30 minutes on days
-6 to -2; cyclophosphamide IV over 15 minutes on day -6; total-body irradiation over
20-30 minutes on day -1; and undergo AHSCT on day 0 (non-myeloablative conditioning).

- Graft-vs-host disease prophylaxis: Patients with related or unrelated donors receive
cyclosporine IV over 2-4 hours or orally on days -3 to 100 followed by a taper,
mycophenolate mofetil IV or orally on days -3 to 46 followed by a taper, and
methotrexate IV on days 1, 3, 6, and 11.

Patients who received umbilical cord blood receive cyclosporine and mycophenolate mofetil as
above (no methotrexate).

Follow-up period of 2 years post-transplant.

DISEASE CHARACTERISTICS:

- Histologically confirmed classical Hodgkin lymphoma, including CD20+ disease

- No lymphocyte predominant histology

- Primary refractory or relapsed disease with all 3 risk factors, failed platinum-based
chemotherapy, or disease relapsed more than 100 days after autologous stem cell
transplantation, proven by biopsy or fine-needle aspiration (cytology) of an involved
site

- Risk factors are defined as B-symptoms, extranodal sites of disease, and disease
remission lasting < 1 year after first-line therapy

- Failed doxorubicin hydrochloride or mechlorethamine hydrochloride-containing
front-line therapy

- Fludeoxyglucose F 18-PET scan demonstrating PET-avid disease

- No more than 2 prior salvage chemotherapy regimens (for patients proceed to allogeneic
hematopoietic stem cell transplantation [AHSCT])

- Donor available meeting 1 of the following criteria (for patients proceed to AHSCT):

- HLA-matched or one allele mismatched related donor

- Genotypically or phenotypically matched at ≥ 9/10 of the A, B, C, DRB1, and
DQB1 loci, as tested by high resolution

- Peripheral blood stem cells (PBSC) collected

- HLA-matched unrelated donor

- Matched at ≥ 9/10 (allele mismatch only) of the A, B, C, DRB1, and DQB1
loci, as tested by high resolution

- PBSC or bone marrow collected

- Umbilical cord blood (2 units)

- must be ≥ 4/6 HLA-A, B antigen, and DRB1 allele matched with recipient

PATIENT CHARACTERISTICS:

- Platelet count > 50,000/mm^3

- ANC > 1,000/mm^3

- Cardiac ejection fraction > 50% (for patients ≥ 18 years of age)

- Fractional shortening > 50% by echocardiogram* (for patients < 18 years of age)

- Adjusted diffusing capacity > 50% on pulmonary function testing*

- Serum creatinine < 1.5 mg/dL

- Creatinine clearance ≥ 50 mL/min

- Total bilirubin < 2.0 mg/dL in the absence of a history of Gilbert disease

- HIV I and II negative

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Karnofsky performance status (PS) ≥ 70% or Lansky PS ≥ 70% (for patients proceed to
AHSCT)

- No active and uncontrolled infection at time of transplantation including active
infection with Aspergillus or other mold (for patients proceed to AHSCT) NOTE:
*measured since last chemotherapy

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior allogeneic transplantation

- No more than 1 prior autologous transplantation

- No inability to complete planned cytoreduction due to therapy complications