An open phase ii study of non-myeloablative allogeneic stem cell transplantation for refractory/recurrent and poor risk haematological malignancy

A. J. Davies, I. N.M. Micallef, D. C. Taussig, J. D. Cavenagh, J. M. Foran, N. McBride, D. Syndercombe-Court, S. M. Kelsey, T. A. Lister, A. Z.S. Rohatiner

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A study of non-myeloablative allogeneic stem cell transplantation (NSCT) forrefactory/ recurrent and poor risk haematological malignancy has been in progress at SBH since Dec 1998. 22 patients (pts.), median age 51 years (range 31-64) have undergone 25 procedures (3 repeated because of autologous haemopoietic reconstitution). 4 pts. had follicular lymphoma (FL), 3 lymphoplasmacytoid (LPC), 3 large B cell lymphoma (LBCL), 2 Hodgkin's disease, 3 multiple myeloma (MM), 2 chronic lymphocytic leukaemia, 3 poor risk acute myeloid leukaemia (AML) and 2 secondary myelodysplasia (MDS). The median number of previous therapies was 4 (range 1-8); at the time of transplant 5 pts. were in CR/ CR(u), 9 in PR, 3 had refractory disease, 2 progressive disease (PD) and 3 MDS (1 AML->MDS). Conditioning comprised Fludarabine 25mg/m2 day -6 to -2 and cyclophosphamide lg/m2 day -3 and -2 (21pts.) or melphalan 140mg/m2 day -2 (4 pts.). Graft versus host disease (GVHD) prophylaxsis comprised standard cyclosporin A and methotrexate. Donor lymphocyte infusions (DLI) were given at 3 months for progressive disease, lack of response or low donor chimerism. Bone marrow was used in 15 cases, peripheral blood in 9 and both in 1. The median number of CD34+ cells infused was 2.52x 106/ Kg (range 0.64-5.70). Neutrophil engraftment was achieved at a median of 17 days (range 11-20). In 10 pts. the platelet count never fell below 20x109/1. Toxicity of the regimen was low with 11 febrile neutropenic episodes, 2 pts. developed pneumocystis pneumonia, 3 self-limiting respiratory viral infections and 4 grade I-II mucositis. Median hospital stay was 19 days (range 12-50). 1 pt. died of hepatic GVHD at day 160 in CR. Marrow donor chimerism (assessed by STR-PCR) was a median of 55% (range 0-100) al day 28, increasing to 67% (range 0-100) at day 100. DLI at a dose of IxlO'/Kg were administered to 10 pts., 4 for PD, 2 for PD with low chimerism and 4 for residual disease with low chimerism. A total of 8 pts. developed GVHD (5 acute, 3 chronic extensive) including 3 pts. following DLI. All had chimerism >50% at the time. With follow-up ranging from 1 month to 1.75 years, all 5 pts. with AML/MDS are in CR, as are 1 pt. with LBCL, 1 with FL and 1 with MM. 8 pts. have progressed, 3 of the latter have died. The 3 pts. who developed chronic GVHD all progressed. Following DLI, 2 pts. with lymphoma have had evidence of response. NSCT is feasible with low early toxicity and short in-patient stay in a group of pts. in whom conventional allografting carries high mortality/morbidity.

Original languageEnglish (US)
Pages (from-to)353b
Issue number11 PART II
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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