Haematologica 2003 - Supplements

210
Monitoring of minimal residual disease in the bone
marrow of patients with multiple myeloma after
allogeneic stem cell transplantation by combined
morphological and cytogenetic analysis
Izhar Hardan, Luba Trakhtenbrot, Rachel Rothman, Malka
Reichard, Avichai Shimoni, Frida Brok-Simoni, Gideon
Rechavi, Ninette Amariglio and Arnon Nagler
The department of Hematology and Bone Marrow Transplantation,
and Pediatric Hemato-Oncology , The Chaim Sheba Medical
Center, Tel-Hashomer; Israel, ; Bio View Ltd., Nes Ziona, Israel
The detection and monitoring of minimal residual disease (MRD)
in patients (pts) with multiple myeloma (MM) after allogeneic
stem cell transplantation (SCT) is crucial for clinical decision
making. The need for DLI or aditional therapy is mainly based on
the determination of disease status at that stage. However, the
definition of CR and MRD status in MM is often difficult and
uncertain. This difficulty also exists when a chromosomal
aberration is found in patients bone marrow. FISH is considered
the study of choice for these abnormalities, however positive
results in the range of up to 10% of bone marrow cells are
frequent (background) . We recently described the use of the
combined morphological and FISH analysis by the DUET
system (Bioview Ltd, Israel) for more precise determination of
the chromosome 13 status in MM pts. By this method we could
determine the lineage of the cells carrying chromosome 13q
deletion (del13q) and detect the true positive FISH signs from
the false positive signs that emerged from non-plasma cells. A
minute population of plasma cells with del13q can be identified
by this system.
Methods: We monitored MRD by the combined system for del
13q or rearrangement at chromosome 11 and 14 in the BM of 7
MM patients (1 in clinical PR, 6 in clinical CR) after reduced
intensity SCT. Complete cytogenetic remission (CCR) was
defined by the absence of plasma cells bearing an aberration.
Results: The patient in PR had a positive study for del13q while
whith 100% donor chimerism defined by microsatellite study. In
4 pts with clinical CR, 2 with 100% chimerism and 2 with mixed
chimerism, CCR was defined and maintained for 18, 16, 12 and 7
months. The chimerism status converted to 100% donor in the
two patients with mixed chimerism 2 and 5 months later. In one
patient whith clinical CR, a CCR was initialy defined, but after 6
months the combined study detected 2% of true positie cells.
During this period the chimerism status was defined 100% donor.
A clinical progression was evident in this patient three months
later. One patient in clinical CR had an initial study whith 1.5 %
positive cells while 100% donor chimerism by microsatellite
study. Immunofixation test converted positie in this patient 4
months later.
Conclusions: The combined morphology and FISH study can
serve as a powerful tool for the precise determination of MRD
status in pts with MM after SCT. This method can overcome
obstacles in the definition of CR that are specific to this group of
patients. Chimerism status may not be an obvious equivalent of
the MRD status in patients with MM after SCT with reduced
intensity conditioning.
7.5 Miscellaneous
211
Interactive Computer Program Reveals Current Disease
Features and Patterns of Myeloma Management
Brian G.M. Durie,1 Michael S. Katz2
1Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA,
2International Myeloma Foundation, N. Hollywood, CA
Beginning in November 2002, an interactive computer program
was initiated at patient seminars conducted by the International
Myeloma Foundation. Real time answers are obtained about
details of myeloma and its treatment. Results from the first 2
seminars, involving over 250 participants, show interesting
trends. The median age was 62 years, but unexpectedly more
patients were women: 54% and 59%. The most common
presenting complaint was bone pain (50%), but 15-20% of
patients were diagnosed following a routine physical examination
or investigation of anemia or fatigue (another 15%). Investigation
of an abnormal serum/urine protein result occurred in 1-5%.
Presentation with renal problems was rare: 1-2%. However,
during the disease course 16% developed an elevated serum
creatinine, which in 26% was associated with use of non-steroidal
anti-inflammatory agents (NSAIDs).Frontline therapy was most
commonly VAD in 35-40%. MP was used in 22%;
Dexamethasone alone in 9-14%; Thalidomide/Dexamethasone in
4-10%. The overall use of Thalidomide was evaluated. Rather
remarkably, Thalidomide plus Dexamethasone was the current
treatment of 27-33% of patients. In addition, 43-48% of patients
had been treated with thalidomide at some time. For 32%, the
maximum dose was 50 or 100mg per day. The wide use of
bisphosphonates was confirmed in 73-85% of patients. 33-45% of
patients had switched from pamidronate (Aredia) to zoledronic
acid (Zometa) in 2002/2003. 23-47% of patients were currently
taking Aredia; 38-50% were taking Zometa. 20% had been taking
a bisphosphonate for > 3 years. Only 4% had stopped taking a
bisphosphonate; 14-15% had modified the dose/schedule/drug
choice. Of note, only 21-29% had received an autotransplant. 4-
8% had undergone stem cell harvesting only. Experimental drugs,
such as Velcade, Revimid/Actimid and Trisenox, were widely
known. Patients are very interested to participate in clinical trials,
(53-63% for Velcade/Revimid/Actimid), but very few have been
able to enroll in trials. Only 2-3% had received Velcade, 0-1%
Revimid/Actimid and 0% Trisenox. Overall survival and quality
of survival were the major priorities for participants. 15-23% had
survived for over 5 years. These ongoing interactive programs
show great promise in providing current information about
disease patterns and trends in myeloma therapy.
212
Estimation of angiogenesis is of prognostic
significance regarding survival in patients with multiple
myeloma.
N.F. Andersen, L. Heickendorff, C. Rask, J.L. Nielsen, T.
Standal, M. Borseth, K. Bendix, N. Abildgaard & F.B.
Sørensen.
Departments of Haematology, Clinical Biochemistry and Pathology,
Aarhus University Hospital, Aarhus, Denmark, and Institute of
Cancer Research, Trondheim, Norway.
Background of the study: The possible significance of bone
marrow angiogenesis in multiple myeloma has recently been
investigated in several studies. Estimates of bone marrow
angiogenesis have been found to be elevated in patients with
S181