Allogeneic Stem Cell Transplantation in Relapsed/Refractory T-, NK/T-cell Lymphomas

Conditioning therapy

• Busulfan (Busulfex®; Patheon Manufacturing Services LLC, Greenville, NC 27834) 3.2 mg/kg + 5% DW (the diluent quantity should be 10 times the volume of Busulfan, so that the final concentration of busulfan becomes approximately 0.5 mg/mL), intravenously for 3 hours once daily for 3 days (days -7 to -5)
• Fludarabine (Fludarabine®, Zydus Hospira Oncology Private Ltd., Ahmedabad, India) 30 mg/m2 + 5% DW 100㎖, intravenously for over 1 hour once daily for 6 days (days -8 to -3)

• Busulfan should be infused as soon as completion of fludarabine infusion

Primary objective of this study I. To determine the 2-year progression-free survival of this reduced toxicity conditioning in relapsed or refractory T- and NK/T-cell non-hodgkin lymphoma patients.

Secondary endpoints I. To evaluate the response rate, engraftment rate and time to engraftment, 2-year overall survival, 100-days treatment-related mortality, regimen-related toxicities by CTCAE version 4.03, post-transplantation complications (HVOD, acute/chronic graft-versus-host disease (GVHD), cytomegalovirus (CMV) infection,CMV disease) of this reduced toxicity conditioning in relapsed or refractory T- and NK/T-cell non-hodgkin lymphoma patients.

Inclusion criteria

• Age 19 - 65
• Histologically confirmed T or NK cell lymphomas :

• anaplastic large cell lymphoma
• angioimmunoblastic T-cell lymphoma,
• peripheral T-cell lymphoma, NOS
• NK/T-cell lymphoma
• Relapsed after or refractory to one or more of previous chemotherapy including frontline autologous HSCT.
• At least one measured lesion using conventional CT or PET CT at the time of relapse after or refractory to one or more of previous chemotherapy and before salvage chemotherapy
• Complete or Partial response after short cycles of salvage chemotherapy
• Patients who have HLA full-match (8/8 in HLA-A, B, C, DR by DNA high-resolution technique) or one-locus mismatch (7/8) sibling, or unrelated bone marrow or peripheral blood or cord blood stem cell donors
• ECOG performance status ≤ 2
• Charlson Comorbidity Index (CCI) before HSCT ≤ 3
• Adequate renal function : serum creatinine level < 2.0 mg/dL
• Adequate liver function :

• Transaminase (AST/ALT) < 3 X upper normal value (or < 5 x ULN in the presence of lymphoma involvement of the liver)
• Total bilirubin < 2 X upper normal value (or < 5 x ULN in the presence of NK/T involvement of the liver)
• Cardiac ejection fraction ≥ 50 % as measured by MUGA or 2D ECHO without clinically significant abnormality
• No clinically significant infection
• No clinically significant bleeding symptoms or sign
• Patients who decided to participate in this study and signed for a written consent

Exclusion criteria

• Adult T cell leukemia/lymphoma, Lymphoblastic lymphoma, Primary cutaneous CD30+ T cell disorders Mycosis fungoides, Sezary SD
• Patients who have previously performed Allo-HSCT
• T cell lymphoma with primary central nervous system (CNS) Involvement.

** However, patients who have only had prophylactic intrathecal or intravenous chemotherapy against CNS disease are eligible.

• Patients with a known history of HIV seropositivity or HCV (+).

** Patients with HBV are eligible. However, primary prophylaxis using antiviral agents is recommended for HBV carrier or prevent HBV reactivation during whole treatment period.

• Any other malignancies within the past 5 years

** Except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri

• Ejection fraction < 50% by a echocardiography
• FEV1 <60% or DLCO <60% by a pulmonary function test
• ECOG performance status 3 or 4
• Combined serious medical problem or disease

• Serious or unstable heart disease although proper treatment
• Myocardial infarction in recent 3 months
• Underlying serious neurologic or psychiatric disease including dementia or seizure
• Active uncontrolled infection including hepatitis B and C
• Serious other medical problems observed by the doctors in charge of the patient
• Pregnant or lactating women, women of childbearing potential not employing adequate contraception