Premium
In vivo depletion of B cells using a combination of high‐dose cytosine arabinoside/mitoxantrone and rituximab for autografting in patients with non‐Hodgkin's lymphoma
Author(s) -
Voso Maria Teresa,
Pantel Gitta,
Weis Mirjam,
Schmidt Petra,
Martin Simona,
Moos Marion,
Ho Anthony D.,
Haas Rainer,
Hohaus Stefan
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.02084.x
Subject(s) - medicine , vincristine , chemoimmunotherapy , mitoxantrone , rituximab , bone marrow , follicular lymphoma , lymphoma , granulocyte colony stimulating factor , chop , chemotherapy , cyclophosphamide , gastroenterology
We performed a pilot study including rituximab (Mabthera; IDEC‐C2B8, Hoffmann‐La Roche) with a sequential high‐dose therapy protocol in 15 patients with follicular and three patients with mantle cell lymphoma and studied the potential of the chemoimmunotherapy to induce depletion of malignant B cells in vivo . Our treatment protocol included induction with three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, followed by peripheral blood stem cell (PBSC) mobilization using high‐dose cytosine arabinoside (2 g/m 2 every 12 h, days 1 and 2) and mitoxantrone (10 mg/m 2 , days 2 and 3) (HAM), preceeded by rituximab (375 mg/m 2 ). The proportion of CD19 + B cells in blood and bone marrow decreased from 1·2 ± 0·4% to 0·13 ± 0·1% ( P = 0·01) and from 2·7 ± 0·8% to 0·8 ± 0·5% ( P = 0·03) respectively. The number of t(14;18)‐positive cells in blood and bone marrow progressively decreased with treatment, as assessed by the quantitative real‐time PCR assay in four patients. Conversion to PCR‐negativity was achieved in the peripheral blood (PB) of seven informative patients. Leucaphereses were performed during the granulocyte colony‐stimulating factor (G‐CSF)‐supported leucocyte recovery phase. In 17 of 18 patients, a median of 15·1 × 10 6 CD34 + cells/kg body weight (BW) could be harvested by a single procedure for enrichment by an immunomagnetic method. Leucapheresis products contained 51·3 ± 28·8 × 10 4 CD19 + B cells/kg BW (mean) and were t(14;18) PCR negative in all seven informative patients. These data compare favourably with results obtained in patients treated with the same regimen without rituximab. The high‐dose therapy ( n = 12 patients), including total body irradiation (14·4 Gy) and cyclophosphamide (200 mg/kg BW), was also preceeded by rituximab. Recovery of neutrophils to > 0·5 × 10 9 /l and of platelets to > 20 × 10 9 /l required a median of 13·5 and 11·5 d (range 11–24 and 9–24 d) respectively. In conclusion, the addition of the CD20 antibody to chemotherapy ensured tumour depletion in vivo and allowed the collection of PBSCs devoid of tumour cells and with conserved engraftment capability.