Bone Marrow Transplantation in Acute or Chronic Leukaemia

Abstract

Using T-depleted BM from HLA-identical sibling donors we have performed 36 BMTs since 5/83 in first remission (CR1) of acute leukaemia (AL). Standard conditioning for BMT consisted of Cy 60 mg/kg×2 and 7.5 Gy single fraction TBI (n = 27). Six patients received Ara-C 3 g/m²×6, Cy 45 mg/kg×2 and 7.5 Gy, while 3 received Cy 60 mg/kg×2 and 8 Gy radiation. T lymphocytes were depleted in vitro with 2 murine McAbs (MBG6 + RFT8, n= 17; or RFT8 + RFT12, n= 13; or RFT2, RFT8 + RFT12, n=6) plus rabbit C’-mediated lysis. No immunosuppressive therapy was given in the absence of graft-versus-host disease (GvHD). Of 34 patients evaluable for aGvHD, 4 had grade I, 2 grade II and 1 grade III. Chronic GvHD occurred in 3 of 22 evaluable patients ( > 150 days). There have been 13 deaths but only 1 from leukaemic relapse (CNS). The mean KS of surviving patients is 86% and actuarial disease-free survival is 53% at 40 months or 65% in those having ‘standard conditioning’. The previous major problems of GvHD and leukaemic relapse appear to have been largely overcome. The major risk factor now is infection, particularly pneumonitis, and this problem is surmountable

Bone Marrow Transplantation

“…Similar results were obtained in Genoa without altering the classical CT -RT sequence [146], so that the better results of HfTBI versus fTBI should not be interpreted as an effect of schedule reversal, but of the hyperfractionation procedure itself. However, fast-dose single-fraction TBI is essential to control the increased graft failure and relapse rate observed after TCO [147], as will be discussed later. Another way of increasing the total radiation dose is incorporated in the split TBI VVRAPIO-X regimen, leaving aside the CT component (vincristine, daunorubicin, cytarabine, teniposide), which was effective in reducing the graft-failure rate following TCO BMT [148].…”

“…In addition, although not exclusively in CML, 3 other, different but intimately related phenomena were shown to be associated with TCD, i.e., delayed haemopoiesis of donor origin, thus allowing a growth advantage to the residual leukaemic cells [311,312], the presence of radiation-induced chromosomal abnormalities in recipient cells [313] and haemopoietic mixed chimaerism [182,183]. It has been postulated that the host biology and the disease burden are different in CML [314], in which the disease is not minimal at the time and identical twin transplantation on the probability of leukaemia relapse. From [320].…”

“…Somewhat surprisingly, the IBMTR study has shown a significantly higher risk of relapse associated with the use of CyA and TCD to prevent GvHD as compared with methotrexate (MTX) in both CR1 and CR2 transplants [385,392]. The question of TCD favouring relapse has already been discussed in the section on CML, where this effect is most apparent; in any case, it is much less evident in ALL [147,[168][169][170] than in the ALs in general [393]. MTX was associated with a 5-fold decrease in Rl in CR1 transplants and a 3-fold decrease in CR2.…”