Outcomes of 44 Patients with Newly Diagnosed Systemic Light-chain Amyloidosis Associated with Deletion 17p

Abstract

Introduction:
Deletion 17p (del 17p) portends a poor prognosis in myeloma, but its significance in light-chain amyloidosis is unknown.

Patients and methods:
We identified patients with light-chain amyloidosis and del 17p at diagnosis, and analyzed presenting characteristics, treatments, and clinical outcomes. All had baseline biopsy results showing amyloid and serologic and marrow studies, including standard fluorescence in-situ hybridization determinations of del 17p using commercial probes. Consensus criteria for hematologic and organ involvement, progression, and response were used. Kaplan-Meier (log rank) analyses and Cox regression analysis of baseline variables were used to identify predictors of overall and progression-free survival (PFS). Six-month landmark analyses were performed to assess the impact of treatment-related variables.

Results:
We identified 44 patients from 7 countries with median marrow and del 17p plasma cells of 22% (range, 3%-100%) and 30% (2%-93%). Ninety-five percent had cardiac involvement, including 44% stage III. Two-thirds of the patients initially received bortezomib-based therapy. Forty-nine percent of patients experienced complete response or very good partial response, with median time to best response of 4 months (range, 1-28 months). Median overall survival and PFS were 49 and 32 months. Cardiac stage and hematologic response were the key predictors of outcomes. Patients with > 50% and ≤ 50% del 17p in clonal plasma cells had median survivals of 28 and 52 months, respectively (P = .08). In landmark analyses, only hematologic response predicted both overall survival and PFS.

Conclusion:
Cardiac stage, hematologic response, and del 17p percentage impact outcomes in these cases. Emphasis should be placed on optimizing supportive care and achieving a deep hematologic response.

Full text

Original Study
Outcome of Patients With Newly Diagnosed
Systemic Light-Chain Amyloidosis Associated
With Deletion of 17p
Sandy W. Wong,
1
Ute Hegenbart,
2
Giovanni Palladini,
3
Gunjan L. Shah,
4
Heather J. Landau,
4
Melissa Warner,
5
Denis Toskic,
5
Arnaud Jaccard,
6
Timon Hansen,
7
Joan Bladé,
8
M. Teresa Cibeira,
8
Efstathios Kastritis,
9
Angela Dispenzieri,
10
Ashutosh Wechalekar,
11
Cindy Varga,
5
Stefan O. Schönland,
2
Raymond L. Comenzo
5
Abstract
We analyzed 44 patients with newly diagnosed systemic light-chain amyloidosis (AL) and del 17p, a rare finding
in AL. Predictors of overall and progression-free survival were cardiac involvement at diagnosis and hema-
tologic response to therapy, respectively. Median survivals of patients with >50% and £50% del 17p plasma
cells were 28 and 52 months (P[.08).
Introduction: Deletion 17p (del 17p) portends a poor prognosis in myeloma, but its significance in light-chain amyloidosis
is unknown. Patients and Methods: We identified patients with light-chain amyloidosis and del 17p at diagnosis, and
analyzed presenting characteristics, treatments, and clinical outcomes. All had baseline biopsy results showing amyloid
and serologic and marrow studies, including standard fluorescence in-situ hybridization determinations of del 17p using
commercial probes. Consensus criteria for hematologic and organ involvement, progression, and response were used.
Kaplan-Meier (log rank) analyses and Cox regression analysis of baseline variables were used to identify predictors of
overall and progression-free survival (PFS). Six-month landmark analyses were performed to assess the impact of
treatment-related variables. Results: We identified 44 patients from 7 countries with median marrow and del 17p
plasma cells of 22% (range, 3%-100%) and 30% (2%-93%). Ninety-five percent had cardiac involvement, including
44% stage III. Two-thirds of the patients initially received bortezomib-based therapy. Forty-nine percent of patients
experienced complete response or very good partial response, with median time to best response of 4 months (range,
1-28 months). Median overall survival and PFS were 49 and 32 months. Cardiac stage and hematologic response were
the key predictors of outcomes. Patients with >50% and 50% del 17p in clonal plasma cells had median survivals of
28 and 52 months, respectively (P¼.08). In landmark analyses, only hematologic response predicted both overall
survival and PFS. Conclusion: Cardiac stage, hematologic response, and del 17p percentage impact outcomes in
these cases. Emphasis should be placed on optimizing supportive care and achieving a deep hematologic response.
Clinical Lymphoma, Myeloma & Leukemia, Vol. -, No. -,---Published by Elsevier Inc. This is an open access article under
the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: AL amyloidosis, Deletion 17p, FISH cytogenetics, Plasma cells, Prognosis
S.O.S and R.L.C. contributed equally to this article, and both should be considered
senior author.
1
Department of Medicine, Division of Hematology and Blood and Marrow Trans-
plantation, University of California, San Francisco, CA
2
Amyloidosis Center, University of Heidelberg, Heidelberg, Germany
3
Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San
Matteo, Pavia, Italy
4
Memorial Sloan Kettering Cancer Center, New York, NY
5
John C. Davis Myeloma and Amyloid Program, Tufts Medical Center, Boston, MA
6
Department of Hematology, CHU Limoges, Centre National de Référence Maladies
Rares, Limoges, France
7
Hematology and Oncology Practice Altona (HOPA), Hamburg, Germany
8
Amyloidosis and Myeloma Unit, Hospital Clínic de Barcelona, IDIBAPS, Barcelona,
Spain
9
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian
University of Athens, School of Medicine, Athens, Greece
10
Division of Hematology, Mayo Clinic, Rochester, MN
11
UK National Amyloidosis Centre, the Royal Free London NHS Foundation Trust,
University College London, London, UK
Submitted: May 30, 2018; Revised: Jul 2, 2018; Accepted: Jul 16, 2018
Address for correspondence: Raymond L. Comenzo, MD, Tufts Medical Center, 800
Washington St, Box 826, Boston, MA 02111
Fax: (617) 636-3175; e-mail contact: rcomenzo@tuftsmedicalcenter.org
2152-2650/Published by Elsevier Inc. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
https://doi.org/10.1016/j.clml.2018.07.292 Clinical Lymphoma, Myeloma & Leukemia Month 2018
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Introduction
Light-chain amyloidosis (AL) is a rare clonal plasma-cell
neoplasm that causes morbidity and mortality through toxic ef-
fects of misfolded light chains and deposition of amyloid fibrils
affecting key organs such as the heart. In multiple myeloma, age,
renal failure, and chromosomal abnormalities are powerful pre-
dictors of overall survival (OS), and deletion 17p (del 17p) is
considered a high-risk abnormality because it has been associated
with shorter survival.
1
However, depth of response to treatment can
mitigate this association and enable those high-risk patients who
experience complete responses (CRs) and negative minimal residual
disease status to live significantly longer.
2
Bone marrow cytogenetic and fluorescence in-situ hybridization
(FISH) studies are part of the standard staging evaluation in mul-
tiple myeloma, but not in other plasma-cell disorders such as
monoclonal gammopathy of undetermined significance. Our un-
derstanding of the role for such studies in AL is evolving.
3,4
Several
retrospective studies have characterized the significance of cytoge-
netic abnormalities in AL.
5-8
Abnormal FISH was identified as a risk
factor for death,
5
and gain 1q21
6
and translocation (11;14)
7,8
have
both been shown to be associated with adverse outcomes. Del 17p is
rarely found in AL patients, occurring at a frequency of 2% to 6%,
5-7
and its significance has not been well defined.
We performed a retrospective analysis of 44 AL patients with del
17p at diagnosis and analyzed the factors affecting outcomes and
survival.
Patients and Methods
This study retrospectively analyzed patients with systemic AL
amyloidosis with del 17p from medical centers in Germany, France,
United Kingdom, Greece, Spain, Italy, and the United States. All
patients had detection of del 17p by FISH due to a plasma-cell
dyscrasia. Patients with concurrent monoclonal gammopathy of
undetermined significance, or smoldering or symptomatic myeloma
(defined as the presence of lytic lesions) and AL at diagnosis were
included. AL patients with del 17p detected at relapse and symp-
tomatic myeloma patients who developed AL at relapse were
excluded. All patient data were deidentified and were obtained from
each center’s institutionally approved database.
Cardiac staging was assessed by the Mayo system.
9
Cardiac, he-
matologic, and renal responses were evaluated by previously pub-
lished criteria.
10-12
All other organs were evaluated by consensus
guidelines.
11
Cytogenetics and FISH studies used standard methods
and probes used for analysis of multiple myeloma chromosomal
abnormalities. Estimates of del 17p percentages were made on the
basis of the percentages of clonal plasma cells in marrow aspirates
and the percentages of cells deemed del 17p positive by cytopa-
thologists at the individual centers.
Epidemiologic and clinical characteristics included age, gender,
cardiac and renal staging, organs involved, echocardiographic esti-
mates of wall thickness, marrow studies, features of monoclonal
gammopathies, serial paraprotein measurements, specific therapies,
hematologic responses, and survival. Results are reported by inten-
tion to treat except as otherwise noted. OS was calculated from the
date of diagnosis to the date of last contact or death; one patient was
censored at the time of heart transplantation. Progression-free
survival (PFS) was defined as date of death, of hematologic pro-
gression, of unsatisfactory response (ie, no response), or of second-
line therapy. We used Kaplan-Meier (log rank) analyses and Cox
regression analysis of baseline variables to identify predictors of OS
and PFS. Six-month landmark analyses were performed to assess the
impact of treatment-related variables. MedCalc Statistical Software
Table 1 Characteristics of 44 Patients
Characteristic Value
Age at diagnosis (years) 65 (38-81)
Male 27 (61%)
Concurrent MGUS or myeloma 5 (11%)
Marrow PCs 22% (3%-100%)
Patients with PC >10% 37 (84%)
Cytogenetics and FISH 100%
del 17p 44 (100%)
del 17p % (n ¼36) 30 (2-93)
t(11;14) 14 (32%)
t(11;14) % (n ¼11) 76 (12-98)
del 13 19 (43%)
del 13 % (n ¼11) 67 (3-96)
Gain 1q21 7 (16%)
With other complex deletions or
gains
6 (14%)
Trisomies 4 (9%)
t(4;14), t(14;16) 4 (9%)
Other IgH rearrangements 2 (5%)
Clonal
l
light-chain isotype 39 (89%)
Involved FLC (mg/L) 295 (10.1-11,300)
dFLC (mg/L) 284 (10-11,292)
Organs Involved
Number 2 (1-5)
Cardiac 42 (95%)
Renal 31 (70%)
Liver/GI 20 (45%)
Soft tissue 16 (36%)
PNS 8 (18%)
AL Cardiac Stage I/II/IIIa/IIIb 3/18/15/6
NT-proBNP (pg/mL) 4076 (59-27,547)
Troponin I or T greater than
threshold
16 (39%)
hs-cTnT (ng/L) (n ¼14) 38 (7-567)
hs-cTnT >14 ng/L 11 (27%)
Echocardiogram IVSd (mm) 14 (9-22)
Renal Stage I/II/III 15/12/4
Proteinuria, g/24 hours 1.9 (0-14.4)
Serum creatinine (mg/dL) 1 (0.4-8.0)
Alkaline phosphatase (mg/dL) 94 (43-1089)
Data are presented as median (range) or n (%) unless otherwise indicated.
Abbreviations: dFLC ¼difference between involved and uninvolved free light chain;
FISH ¼fluorescence in-situ hybridization; FLC ¼free light chain; hs-cTnT ¼highly sensitive
cardiac troponin T; MGUS ¼monoclonal gammopathy of undetermined significance;
NT-proBNP ¼N-terminal pro b-type natriuretic peptide; PC ¼plasma cell.
2
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Clinical Lymphoma, Myeloma & Leukemia Month 2018
Systemic Light-Chain Amyloidosis

version 17.9.6 (MedCalc Software, Ostend, Belgium; http://www.
medcalc.org; 2017) was used for all statistical analyses.
Results
Patients
Fifty-one cases of AL with del 17p detected in marrow plasma
cells were collected from Germany (n ¼17), France (n ¼7), the
United Kingdom (n ¼2), Spain (n ¼1), Greece (n ¼1), Italy
(n ¼1), and the United States [Mayo Rochester (n ¼9), Memorial
Sloan Kettering Cancer Center (n ¼7), and Tufts Boston (n ¼6)].
Two cases with incomplete survival data and 5 cases of del 17p
detected at relapse were excluded from further analyses. Charac-
teristics of the 44 patients included are shown in Table 1. Patients
were diagnosed between January 19, 2007, and May 30, 2016.
Median follow-up of survivors was 31 months (range, 16-61
months).
Cardiac involvement was present in 95% of patients, and 48%
had stage III disease. The median number of marrow plasma cells
was 22% (range, 3%-100%), and 84% had 10%. All had del 17p
identified by FISH in marrow plasma cells; percentages of plasma
cells containing del 17p were available for 36 patients, and the
median was 30% (range, 2%-93%). Concomitant t(11;14), del 13,
or gain 1q21 was observed in 32%, 45%, and 16% of patients.
Chromosomal aberrations involving t(4;14) or t(14;16) were seen in
9% of patients.
Treatments and Response
For first-line therapy, patients received a bortezomib-based
regimen (n ¼28), dexamethasone and cyclophosphamide or
melphalan (n ¼9), and dexamethasone and lenalidomide (n ¼4),
or underwent stem-cell transplantation (SCT, n ¼3). Nine patients
underwent SCT after induction; therefore, 12 patients received
SCT. Sixteen patients received second-line therapy; a variety of
regimens were used including bortezomib based (n ¼10, 5 of
whom were naive to bortezomib), thalidomide (n ¼2), cyclo-
phosphamide (n ¼1), bendamustine (n ¼2), and melphalan
(n ¼1), all with dexamethasone.
Hematologic responses to first-line therapy were scored in 39
patients [CR/very good partial response (VGPR) 19, partial
response 14, no response 6]. Median time to best response was
Figure 1 Median OS and PFS. (A) OS and (B) PFS of 44 Patients With AL and del 17p at Diagnosis, Showing Median OS of 49 Months
and PFS of 32 Months. (C) Patients With >50% del 17p Marrow Plasma Cells, Although Small in Number (n [12), Exhibited
Trend Toward Shorter Survival (Median, 28 and 52 Months). (D) Survival Curve of Patients With Either t(11;14) or Gain 1q21
Exhibited Trend Toward Shorter Survival (Median, 28 and 53 Months)
0
20
40
60
80
100
01224364860
Time (months)
OS at risk
44 33 28 17 12 3
0
20
40
60
80
100
01224364860
Months
PFS at risk
44 26 19 8 5 2
0
20
40
60
80
100
01224364860
Time (months)
Number at ri sk
< 50% del 17p
24 19 16 9 7 2
> 50% del 17p
12 8 7 3 2 0
P = 0.08
0
20
40
60
80
100
0 1224364860
Time (months)
Numbe r at risk
Neither
19 17 15 12 9 2
Either t(11;14) or gain 1q21
19 13 10 4 3 1
P = 0.06
AB
DC
OS (%)
OS (%)
OS (%) PFS (%)
Abbreviations: AL ¼light-chain amyloidosis; OS ¼overall survival; PFS ¼progression-free survival.
Sandy W. Wong et al
Clinical Lymphoma, Myeloma & Leukemia Month 2018
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4 months (range, 1-28 months). Of 25 cases evaluable for cardiac
responses, 28% (n ¼7) experienced them, and of 23 cases evaluable
for renal responses, 26% (n ¼6) experienced them. Median OS and
PFS were 49 months (range, 0.5-69 months) and 32 months (range,
0.5-67 months), respectively (Figure 1A and B). Two-year OS was
67%. Del 17p most commonly occurred with other cytogenetic
aberrations such as del 13, t(11;14), and gain 1q21. There was no
correlation between the copresence of these abnormalities and the
percentage of plasma cells. However, patients with either or both
t(11;14) or gain 1q21 exhibited a trend toward shorter survival;
median survivals with either or neither of these abnormalities were
28 and 53 months, respectively (Figure 1C). Patients with >50%
del 17p marrow plasma cells, although small in number (n ¼12),
also exhibited a trend toward shorter survival compared to those
with 50%; medians were 28 and 52 months, respectively
(Figure 1D). One case in our series was notable because of clonal
evolution into a leukemic phase with progressive amyloidosis and is
described in Supplemental Data S1 in the online version.
Predictors of PFS and OS
Patients who received bortezomib-based initial treatment had a
similar OS compared to those who received alternative first-line
therapies (Figure 2A), while those receiving SCT had significantly
better OS than those who were not treated with SCT (Figure 2B);
however, patients who underwent SCT were younger and had less
advanced cardiac involvement. SCT patients were a median of 60
years old (range, 38-65 years) and were from Germany (n ¼6),
United States (n ¼5), and the United Kingdom (n ¼1). Seven
were cardiac stage II and three were stage IIIa. Hematologic re-
sponses in these 12 patients were CR/VGPR (n ¼7), partial
response (n ¼4), and no response (n ¼1).
We performed a Cox regression analysis with baseline variables
including age at diagnosis, gender, percentage of marrow plasma
cells, free light chains, cardiac stage, renal stage, liver involvement,
and autonomic and peripheral nervous system involvement in order
to identify predictors of OS. Cardiac stage was the only significant
baseline predictor of OS (P<.05) (Figure 2C). We also performed
6-month landmark Cox regression analyses that included hemato-
logic response to initial therapy, seeking predictors of PFS and OS.
Hematologic response was the only significant predictor of duration
of PFS and of OS in the landmark analyses (Figure 2D).
Discussion
Chromosomal abnormalities as predictors of response and sur-
vival in multiple myeloma have been well described, and their sig-
nificance continues to be refined. The Revised International Staging
System has incorporated cytogenetic data into the risk stratification
for myeloma at diagnosis.
1
Although myeloma and AL are both
Figure 2 Survival According to Treatment With Bortezomib or Alternative First-Line Therapy. (A) Survival curves of Patients Initially
Treated With Either Bortezomib or Other Therapies Overlap, Indicating That Initial Therapy With Bortezomib did Not Provide
Significant Survival Advantage to Patients in This Small Cohort. (B) OS of Patients Who Underwent SCT compared to Those
Who did Not showed Favorable Outcomes for SCT Patients (P<.05); However, Patients Who Underwent SCT Were Younger
and Had Less Advanced Cardiac Involvement. (C) Six-Month landmark Analysis of OS Based on Hematologic Response,
Indicating that Patients With Responsive Disease (CR/VGPR, PR) Had Better Survival Than Those With Nonresponsive (Not
Reported, NR) Disease (P<.05). (D) OS As Function of Cardiac Stage, Predictor of OS by Cox Regression Analysis (P<.05)
Abbreviations: CR ¼complete response; OS ¼overall survival; PR ¼partial response; SCT ¼stem cell transplantation ; VGPR ¼very good partial response.
Systemic Light-Chain Amyloidosis
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Clinical Lymphoma, Myeloma & Leukemia Month 2018

plasma-cell malignancies, the role of such abnormalities cannot be
extrapolated from one to the other because of the differences in the
distribution of chromosomal abnormalities in these two diseases and
because of the different ways these diseases affect organ function.
Translocation (11;14), for example, is present at diagnosis in 20%
of myeloma patients and in >50% of AL patients. Del 17p in
myeloma is present in about 10% of myeloma patients at diagnosis,
and its prognostic impact depends in part on the percentage of
clonal plasma cells with del 17p.
13
Del 17p is rare in AL patients,
hence the need for this collaborative effort. In both myeloma and
AL, however, it is the case that the percentage of clonal cells with del
17p (50% or >50%) and depth of hematologic response are key
predictors of OS.
2,13
Advanced cardiac involvement in AL patients at diagnosis re-
mains a challenge, and despite improved outcomes over the past 15
years, it continues to cause early death in 25% of patients within 6
months of diagnosis.
14
Recently a report on 1551 AL patients seen
between 2000 and 2014 noted that among the 525 treated between
2010 and 2014 who had a median of 10% marrow plasma cells,
75% had cardiac involvement, 66% experienced CR or VGPR, and
38% of those receiving non-SCT chemotherapy survived at 4
years.
14
In this series of 44 AL patients with del 17p at diagnosis
who had a median of 22% marrow plasma cells, 93% had cardiac
involvement, 49% experienced CR or VGPR (25% had SCT and
75% non-SCT therapy), and 50% survived at 49 months. Super-
ficially, then, there does not appear to be a generic detriment with
respect to OS associated with del 17p at diagnosis in AL patients.
In this series, the critical determinants of OS in AL remain car-
diac involvement and hematologic response, although patients with
>50% del 17p plasma cells exhibit a trend toward shorter survival,
as do those with the additional chromosomal abnormalities t(11;14)
or gain 1q. We collaborated on this effort in order to identify the
features of newly diagnosed systemic AL amyloidosis associated with
del 17p, and although these findings require further evaluation in
larger patient series and in clinical trials, they provide guidance to
practitioners caring for patients with AL. The single case of pro-
gression to a leukemic phase with relapsed AL (Supplemental Data
S1 in the online version) illustrates that rarely a more aggressive
clone may emerge from an AL patient harboring del 17p at diag-
nosis. Interestingly, the only AL amyloidosis cell lines
15
that have
been generated to date (from a single patient) also harbor del 17p,
which suggests that this chromosomal aberration in certain situa-
tions may endow AL plasma cells with stromal independence and
proliferative capacity.
Conclusion
We characterize the outcomes of newly diagnosed AL amyloidosis
patients with del 17p. OS in these patients is determined by cardiac
involvement and hematologic response, with the latter also deter-
mining PFS. Patients with >50% del 17p plasma cells and those
with additional cytogenetic abnormalities such as t(11;14) or gain
1q may be at risk for shorter survival. Hematologic and organ re-
sponses, as well as OS and PFS, appear to be similar to previous
reports.
14,16
In rare instances, del 17p may be associated with the
emergence of an aggressive plasma-cell clone.
Clinical Practice Points
Cytogenetic abnormalities are risk factors in multiple myeloma
that affect hematologic response and survival.
In systemic AL, abnormalities such as translocation (11;14) and
gain 1q may affect hematologic response.
In myeloma, del 17p is considered high risk and a marker of poor
prognosis, but its impact, if any, in AL is unclear.
The finding of del 17p in a newly diagnosed AL patient may
perplex the practitioner with respect to prognosis, particularly in
patients with multiorgan involvement.
Unlike factors such as age and renal failure in myeloma and
extent of cardiac damage and intractable hypotension in AL, the
finding of del 17p in a newly diagnosed patient with AL can
create uncertainty regarding the choice and duration of initial
therapy and the use of melphalan in stem-cell transplantation.
Our analysis of this 44-patient case series indicates that cardiac
involvement and hematologic response to therapy are the key
predictors of OS and PFS, and that patients with >50% clonal
plasma cells with del 17p may be at risk for shorter survival.
Key practice points are to optimize supportive care and seek an
early and deep hematologic response.
The initial choice of therapy can be high-dose melphalan if the
baseline clonal plasma-cell percentage is <10%.
If a combination chemotherapy regimen is chosen as an initial
therapy, and if there is no significant hematologic response, a
change in therapy should be considered.
Acknowledgments
The authors thank the clinical research coordinators who
contributed to this study. For their continued support, we also
thank the Division of Hematology-Oncology and the Departments
of Medicine and Pathology and Laboratory Medicine at Tufts, the
Amyloidosis and Myeloma Research Fund at Tufts, the Cam Neely
and John Davis Myeloma Research Fund, the John C. Davis Pro-
gram for Myeloma and Amyloid at Tufts, the Sidewater Family
Fund, the Lavonne Horowitz Trust, the Werner and Elaine
Dannheiser Fund for Research on the Biology of Aging of the
Lymphoma Foundation, David and Barbara Levine (in memoriam),
and the Demarest Lloyd Jr Foundation.
Disclosure
The authors have stated that they have no conflicts of interest.
Supplemental Data
Supplemental data, including figures, accompanying this article
can be found in the online version at https://doi.org/10.1016/j.clml.
2018.07.292.
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Supplemental Figure S1 Clonal Evolution of Disease Into Leukemic Phase. (A) Lambda FLC, BNP, and LDH levels over course of
Therapy. (B) Circulating plasma cells. (C) Clonal plasma-Cell Infiltration of lungs
Abbreviations: AL ¼light-chain Amyloidosis; BNP ¼b-type Natriuretic peptide; Bor ¼bortezomib; BorTD ¼bortezomib, thalidomide, dexamethaso ne; CyBorD ¼cyclophosphamide, bortezomib, and
dexamethasone; FLC ¼free light chain; LC ¼light chain; LDH ¼lactate dehydrogenase; VTD-PACE ¼multidrug regimen containing bortezomib, Thalidomide, dexamethasone, cisplatin, doxorubicin,
cyclophosphamide, and etoposide.
Supplemental Data S1
Supplemental Figure S1A shows the course of a 72-year-old
woman diagnosed with amyloidosis and del 17p; a leukemic phase
occurred at relapse on about day 400. The patient’s disease initially
responded to first-line therapy with CyBorD, but she then experi-
enced relapse despite maintenance bortezomib. At diagnosis, there
were 40% lambda-restricted plasma cells in the marrow with 3% del
17pepositive cells. At progression to leukemic phase, peripheral
blood white blood cell count was 15,100/
m
L with 9% circulating
plasma cells. CD138-selected FISH studies revealed complex chro-
mosomal abnormalities including del 17p in 91% of cells. At
postmortem, significant amyloid deposits and tissue infiltration with
clonal plasma cells were observed. Supplemental Figure S1A shows
the lambda FLC, BNP, and lactate dehydrogenase levels over the
course of therapy, with annotations along the top showing treat-
ments received until death on about day 500. Supplemental
Figure S1B shows the peripheral blood smear containing circu-
lating plasma cells. Supplemental Figure S1C shows a slide stained
for lambda light-chain cells revealing the infiltration of lambda-
restricted plasma cells in lung (brown cells; 50magnification)
Abbreviations: BNP ¼b-type natriuretic peptide; CyBorD ¼
cyclophosphamide, bortezomib, and dexamethasone; FISH ¼fluo-
rescence in-situ hybridization; FLC ¼free light chain;
VTD-PACE ¼multidrug regimen containing bortezomib, thalid-
omide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide,
and etoposide
Sandy W. Wong et al
Clinical Lymphoma, Myeloma & Leukemia Month 2018
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