Blood, 1 February 2003, Vol. 101, No. 3, pp. 1201-1201
CORRESPONDENCE
To the editor:
Graft versus myeloma may overcome the unfavorable effect of
deletion of chromosome 13 in multiple myeloma
Partial or complete deletion of chromosome 13 (del13) is
considered one of the most important prognostic factors for multiple myeloma (MM).1-4 The impact of del13 on the outcome of
allogeneic stem cell transplantation is unknown. We describe 2 patients
with unfavorable MM who benefited from a graft-versus-myeloma effect, resulting in sustained molecular remissions.5
Retrospectively a del13 was found in the diagnostic bone marrow (BM)
aspirates of both patients.
The first patient progressed from monoclonal gammopathy of undetermined
significance (MGUS; diagnosed in 1982) to MM (1991, IgA 
,
stage IIIA). She was refractory to
melphalan+prednisone, and in March 1992 at age 48 she
received a partial T-cell-depleted (1 × 105 T cells/kg)
BM transplant from her HLA-identical sister after conditioning with
cyclophosphamide (120 mg/kg) and total body irradiation (12 Gy). This
was complicated by transient acute graft-versus-host disease (GVHD),
grade I. At the time of transplantation, her BM contained 55% myeloma
cells. After achieving a partial remission (PR; disappearance of M
protein, 8% residual BM cells), she relapsed 8 months after
transplantation: reappearance of M protein, increasing 10 months later
to 20g/L, 30% BM infiltration. She then received donor lymphocyte
infusions (DLIs), 3.3 × 108 T cells/kg. DLIs
were complicated by severe extensive chronic GVHD of skin and
joints. Since May 1994 she is in complete clinical and molecular
remission as demonstrated by absence of M protein, normalization of BM,
and quantitative allele-specific oligonucleotide (ASO)-PCR6 (sensitivity to detect 1 tumor of 1 × 105 normal cells). Molecular remission was
demonstrated in 8 subsequent BM aspirates.
The second patient (stage IIIA, IgG 
) presented with bone pain and
diplopia. His BM showed a 99% infiltration, labeling index 3%, and
2-microglobulin level of 5 mg/mL. The liquor
was infiltrated with plasmablastic cells. He achieved a PR after
induction with intermediate-dose melphalan7 but relapsed
just before allogeneic (allo)-BMT. In the liquor a persistent
M protein of 1 g/L was found after treatment with methotrexate and
cytarabine intrathecally. Evaluation 6 months after transplantation
showed a complete clinical remission. Residual myeloma cells however
could be detected by quantitative ASO-PCR until 36 months after
transplantation (Figure 1). Double-color FISH was performed on thawed cytocentrifuged BM cells,
which had been prepared from diagnostic samples and had been stored at
20°C. A del13 was found in 99 of 100 myeloma cells of patient 1 and
in 35 of 100 myeloma cells of patient 2.
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| Figure 1.
Longitudinal measurement of disease activity in a MM
patient with del13.
The patient presented with a combination a unfavorable prognostic
features including del13. After allogeneic bone marrow transplantation
performed during relapse, he went into sustained clinical (A) and
molecular (B) remission. Remarkable residual MM cells were detected by
quantitative PCR more than 3 years after disappearance of myeloma
proteins (B).
|
|
The 2 patient histories demonstrate that alloreactivity may overcome
the prognostic unfavorable impact of del13 in myeloma. The first
patient is in molecular remission more than 10 years after allo-BMT and
8 years after DLIs. The second patient presented with a combination of
adverse prognostic factors including a high 2-microglobulin level, high labeling index, and
meningeal infiltration. He received a transplant in relapse
after a very short period of remission. Remarkable, quantitative PCR
became negative not until 3 years after transplantation.
Our results suggest that in patients with del13 a search for an
HLA-identical family or unrelated donor is justified. The promising
results of nonmyeloablative allo-SCT in MM8,9 justify inclusion of patients in such protocols as soon as unfavorable factors
are identified after diagnosis.
Laurens Laterveer, Leo F. Verdonck, Ton Peeters, Erik Borst, Andries C. Bloem, and Henk M. Lokhorst
Correspondence: H. M. Lokhorst, Department of
Hematology, University Medical Center Utrecht, HP G03647 Heidelberglaan
100, 3584 CX The Netherlands; e-mail:
h.lokhorst{at}azu.nl
References
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