Haematologica 2003 - Supplements

patients had 100% engraftment of donor cells (including 4
recipients of unrelated donor grafts). One patient died before day
30 from tumor lysis and toxicity. Seven patients achieved
complete remission, and 5 failed to respond. At the time of the
report 6 patients were alive between 3 and 24 months after
transplant (median, 18 months), two in continued complete
remission. The major causes of treatment failure in this group of
refractory and heavily pretreated patients was GVHD (n=4) and
disease (n=2) Thus engraftment of allogeneic progenitor cells
after non myeloablative therapies is feasible in patients with
myeloma, and further exploration of this strategy in patients with
less advanced disease is warranted.
The Seattle group has pioneered an innovative approach to nonablative
transplantation using low dose TBI at a dose of 200 cGy
in a single fraction in conjunction with post transplant immune
suppression with cyclosporine and mycophenolate mofetil. (14)
In the initial experience patients with myeloma and CML who
had not received prior intensive therapy had a high risk of graft
rejection and autologous reconstitution of over 20%. (15) To
improve upon these outcomes, the Seattle group explored the
safety and efficacy of high dose melphalan with autologous stem
cell support followed 90-120 days by a non ablative preparative
regimen of 200 cGy of TBI followed by an allogeneic peripheral
blood stem cell infusion from an HLA identical sibling for
myeloma patients who had never received a prior autograft.
Twelve patients were treated with a median age 49 years (42-63)
with a median time to transplant of 12 months (range, 4-57
months). Toxicity from the allografting was minimal with a
median of 0 days of neutropenia (range, 0-10) and a median nadir
neutrophil count of 760 neutrophils/l (range, 150-1270
neutrophils/l. All patients had donor cell engraftment with a
median percentage of donor cells of 82%. Six patients developed
grade III acute GVHD and 2 developed grade IV GVHD. Seven
patients achieved a CR and 3 patients have died, 9 patients were
alive with a median follow up of 7 months at the time of the
report. (16)
Further evidence for the role of non-ablative preparative regimens
for multiple myeloma is provided by the number of papers
presented in the 42 nd Annual Meeting of the American Society of
Hematology (Table 1).
Table 1: Other Non Ablative Stem Cell Transplant Trials with
>10 Myeloma Patients Reported at the 42 nd Annual Meeting of
the American Society of Hematology.
Ref N Age Regimen Graft
Failure
NRM PFS
16 50 48
(33-62)
17 23 47
(34-58)
18 22 54
(32-66)
19 16 57
(42-70)
FM:25
FB:17
FM-
Campath
FC-200
cGy
NS Good
Risk
10%
Poor
Risk
20%
0 17%
@ 1yr
1 27%
@
100d
Mel 100 1 3/16
Good
Risk
80%
Poor
Risk
27%
42%
@ 1yr
Of interest among the papers presented are the results reported to
the EBMT in which patients with good risk disease
(chemosensitive relapse or remission consolidation) had a 10%
non relapse mortality and a progression free survival of 80%. (17)
In all reported series to date GVHD is an important cause of
treatment failure. The use of pretransplant CAMPATH 1H has
been reported to decrease the incidence of this complication,
according to the experience reported by Peggs et al. (18)
Melphalan at a lower dose of 100 mg/m 2 has also been used as a
preparative regimen for non-ablative or reduced intensity
conditioning. This dose as reported by the University of Arkansas
group results in high rates of engraftment and low incidence of
toxicity in patients who relapsed after either one or two
autologous transplants. (19,20) All studies to date have
demonstrated that chemosensitivity as well as extent of prior
therapies are important prognostic factors for outcomes with few
patients with refractory disease obtaining long term disease
control.
SUMMARY: The goals of therapy for myeloma have changed
substantially from the initial days of melphalan and prednisone.
(21) The advent of autologous transplant, and the recognition of
the graft versus myeloma effect make it possible to search for
complete remission and long term disease control in a substantial
proportion of myeloma patients. However, the ability to exploit
the graft versus myeloma effect has been hampered by the high
incidence of transplant related mortality seen in the myeloma
population. Reducing the intensity of the preparative regimen has
been explored as a strategy to improve the outcomes of allogeneic
transplant in myeloma. The results of the limited experience to
date demonstrate that non-ablative and reduced intensity
conditioning regimens are feasible in myeloma. This procedure
results in donor cell engraftment, acceptable toxicity, and long
term disease control in a fraction of patients. However, graft
versus host disease and disease recurrence particularly in patients
with relapsed or refractory disease continue to be the major
obstacles to overcome. Further studies will be needed to define
the role of reduced intensity and non-ablative conditioning in the
treatment of multiple myeloma.
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