Incidence of multiple myeloma among cleanup workers of the chornobyl accident and their survival
The study presents the updated data on the multiple myeloma (MM) incidence in Ukrainian cleanup workers after the Chornobyl accident and their survival. The epidemiological analysis is based on the extended follow-up period to identify new MM cases for higher statistical power and to collect additio...
Збережено в:
| Опубліковано в: : | Experimental Oncology |
|---|---|
| Дата: | 2016 |
| Автори: | , , , , , , , , , |
| Формат: | Стаття |
| Мова: | English |
| Опубліковано: |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2016
|
| Теми: | |
| Онлайн доступ: | https://nasplib.isofts.kiev.ua/handle/123456789/137696 |
| Теги: |
Додати тег
Немає тегів, Будьте першим, хто поставить тег для цього запису!
|
| Назва журналу: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Цитувати: | Incidence of multiple myeloma among cleanup workers of the chornobyl accident and their survival / D. Bazyka, N. Gudzenko, I. Dyagil, N. Trotsiuk, E. Gorokh, Z. Fedorenko, V. Chumak, E. Bakhanova, I. Ilienko, A. Romanenko // Experimental Oncology. — 2016 — Т. 38, № 4. — С. 267-271. — Бібліогр.: 20 назв. — англ. |
Репозитарії
Digital Library of Periodicals of National Academy of Sciences of Ukraine| id |
nasplib_isofts_kiev_ua-123456789-137696 |
|---|---|
| record_format |
dspace |
| spelling |
Bazyka, D. Gudzenko, N. Dyagil, I. Trotsiuk, N. Gorokh, E. Fedorenko, Z. Chumak, V. Bakhanova, E. Ilienko, I. Romanenko, A. 2018-06-17T15:11:23Z 2018-06-17T15:11:23Z 2016 Incidence of multiple myeloma among cleanup workers of the chornobyl accident and their survival / D. Bazyka, N. Gudzenko, I. Dyagil, N. Trotsiuk, E. Gorokh, Z. Fedorenko, V. Chumak, E. Bakhanova, I. Ilienko, A. Romanenko // Experimental Oncology. — 2016 — Т. 38, № 4. — С. 267-271. — Бібліогр.: 20 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/137696 The study presents the updated data on the multiple myeloma (MM) incidence in Ukrainian cleanup workers after the Chornobyl accident and their survival. The epidemiological analysis is based on the extended follow-up period to identify new MM cases for higher statistical power and to collect additional data on the disease course and outcome for the survival analysis. The objective of the study was to analyze the MM incidence and survival in Chornobyl cleanup workers in 1996–2013 in comparison with the national MM statistical data. Materials and Methods: A study cohort consisted of 152,520 male cleanup workers resided in one of 6 regions of Ukraine or Kyiv city and registered in the Ukrainian State Chornobyl Registry (SChR). The Cohort Database was linked to the Ukrainian National Cancer Registry (NCR) Database to identify MM cases and to analyze MM incidence in 1996– 2013. Standardized incidence ratios (SIR) for MM over the period 1996–2013 were calculated as compared to the general population of Ukraine. A 10-year lag period (when incident cases are not considered radiation-related) was applied. One-year and 5-year cause-specific survival of MM cases were calculated as percentage of those who were alive correspondingly for 1 or 5 years after diagnosis among overall diagnosed. By the moment, the 5-year survival rate either for the sub-period 2008–2013 or for the whole study period 1996–2013 cannot be determined. Vital status data were updated according to the recent SChR and NCR information. Results: 75 MM cases diagnosed in 1986–2013 were identified in the studied cohort. 69 of them were included to the incidence analysis considering a 10-year lag period. While the incidence over 15 years after the accident did not differ significantly from the corresponding rate in general population of Ukraine, a tendency to increase was seen in the period from 16 to 21 years after the accident, and significantly increased SIR estimate was revealed for 2008–2013 (SIR 1.86, 95% confidence interval (CI) 1.27–2.44). The highest incidence was detected in 2008–2013 among cohort members diagnosed over the age of 50 years mostly due to the significant excess among those aged 60–69 (SIR 2.46, 95% CI 1.32–3.59). Survival rates in cleanup workers were shown to be higher than in the general population of Ukraine (73.9% and up to 65.0%, respectively). Conclusions: SIR for the 2008– 2013 period, 22–27 years after the accident, demonstrated the significant excess of MM incidence among male cleanup workers. Survival of MM cases is higher in cleanup workers in comparison with that in general population. This article is a part of a Special Issue entitled “The Chornobyl Nuclear Accident: Thirty Years After”. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions Incidence of multiple myeloma among cleanup workers of the chornobyl accident and their survival Article published earlier |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| title |
Incidence of multiple myeloma among cleanup workers of the chornobyl accident and their survival |
| spellingShingle |
Incidence of multiple myeloma among cleanup workers of the chornobyl accident and their survival Bazyka, D. Gudzenko, N. Dyagil, I. Trotsiuk, N. Gorokh, E. Fedorenko, Z. Chumak, V. Bakhanova, E. Ilienko, I. Romanenko, A. Original contributions |
| title_short |
Incidence of multiple myeloma among cleanup workers of the chornobyl accident and their survival |
| title_full |
Incidence of multiple myeloma among cleanup workers of the chornobyl accident and their survival |
| title_fullStr |
Incidence of multiple myeloma among cleanup workers of the chornobyl accident and their survival |
| title_full_unstemmed |
Incidence of multiple myeloma among cleanup workers of the chornobyl accident and their survival |
| title_sort |
incidence of multiple myeloma among cleanup workers of the chornobyl accident and their survival |
| author |
Bazyka, D. Gudzenko, N. Dyagil, I. Trotsiuk, N. Gorokh, E. Fedorenko, Z. Chumak, V. Bakhanova, E. Ilienko, I. Romanenko, A. |
| author_facet |
Bazyka, D. Gudzenko, N. Dyagil, I. Trotsiuk, N. Gorokh, E. Fedorenko, Z. Chumak, V. Bakhanova, E. Ilienko, I. Romanenko, A. |
| topic |
Original contributions |
| topic_facet |
Original contributions |
| publishDate |
2016 |
| language |
English |
| container_title |
Experimental Oncology |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| format |
Article |
| description |
The study presents the updated data on the multiple myeloma (MM) incidence in Ukrainian cleanup workers after the Chornobyl accident and their survival. The epidemiological analysis is based on the extended follow-up period to identify new MM cases for higher statistical power and to collect additional data on the disease course and outcome for the survival analysis. The objective of the study was to analyze the MM incidence and survival in Chornobyl cleanup workers in 1996–2013 in comparison with the national MM statistical data. Materials and Methods: A study cohort consisted of 152,520 male cleanup workers resided in one of 6 regions of Ukraine or Kyiv city and registered in the Ukrainian State Chornobyl Registry (SChR). The Cohort Database was linked to the Ukrainian National Cancer Registry (NCR) Database to identify MM cases and to analyze MM incidence in 1996– 2013. Standardized incidence ratios (SIR) for MM over the period 1996–2013 were calculated as compared to the general population of Ukraine. A 10-year lag period (when incident cases are not considered radiation-related) was applied. One-year and 5-year cause-specific survival of MM cases were calculated as percentage of those who were alive correspondingly for 1 or 5 years after diagnosis among overall diagnosed. By the moment, the 5-year survival rate either for the sub-period 2008–2013 or for the whole study period 1996–2013 cannot be determined. Vital status data were updated according to the recent SChR and NCR information. Results: 75 MM cases diagnosed in 1986–2013 were identified in the studied cohort. 69 of them were included to the incidence analysis considering a 10-year lag period. While the incidence over 15 years after the accident did not differ significantly from the corresponding rate in general population of Ukraine, a tendency to increase was seen in the period from 16 to 21 years after the accident, and significantly increased SIR estimate was revealed for 2008–2013 (SIR 1.86, 95% confidence interval (CI) 1.27–2.44). The highest incidence was detected in 2008–2013 among cohort members diagnosed over the age of 50 years mostly due to the significant excess among those aged 60–69 (SIR 2.46, 95% CI 1.32–3.59). Survival rates in cleanup workers were shown to be higher than in the general population of Ukraine (73.9% and up to 65.0%, respectively). Conclusions: SIR for the 2008– 2013 period, 22–27 years after the accident, demonstrated the significant excess of MM incidence among male cleanup workers. Survival of MM cases is higher in cleanup workers in comparison with that in general population. This article is a part of a Special Issue entitled “The Chornobyl Nuclear Accident: Thirty Years After”.
|
| issn |
1812-9269 |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/137696 |
| citation_txt |
Incidence of multiple myeloma among cleanup workers of the chornobyl accident and their survival / D. Bazyka, N. Gudzenko, I. Dyagil, N. Trotsiuk, E. Gorokh, Z. Fedorenko, V. Chumak, E. Bakhanova, I. Ilienko, A. Romanenko // Experimental Oncology. — 2016 — Т. 38, № 4. — С. 267-271. — Бібліогр.: 20 назв. — англ. |
| work_keys_str_mv |
AT bazykad incidenceofmultiplemyelomaamongcleanupworkersofthechornobylaccidentandtheirsurvival AT gudzenkon incidenceofmultiplemyelomaamongcleanupworkersofthechornobylaccidentandtheirsurvival AT dyagili incidenceofmultiplemyelomaamongcleanupworkersofthechornobylaccidentandtheirsurvival AT trotsiukn incidenceofmultiplemyelomaamongcleanupworkersofthechornobylaccidentandtheirsurvival AT gorokhe incidenceofmultiplemyelomaamongcleanupworkersofthechornobylaccidentandtheirsurvival AT fedorenkoz incidenceofmultiplemyelomaamongcleanupworkersofthechornobylaccidentandtheirsurvival AT chumakv incidenceofmultiplemyelomaamongcleanupworkersofthechornobylaccidentandtheirsurvival AT bakhanovae incidenceofmultiplemyelomaamongcleanupworkersofthechornobylaccidentandtheirsurvival AT ilienkoi incidenceofmultiplemyelomaamongcleanupworkersofthechornobylaccidentandtheirsurvival AT romanenkoa incidenceofmultiplemyelomaamongcleanupworkersofthechornobylaccidentandtheirsurvival |
| first_indexed |
2025-11-25T23:54:25Z |
| last_indexed |
2025-11-25T23:54:25Z |
| _version_ |
1850589218244395008 |
| fulltext |
Experimental Oncology ��� �������� ���� ��ecem�er���� �������� ���� ��ecem�er� ��ecem�er� ���
INCIDENCE OF MULTIPLE MYELOMA AMONG CLEANUP WORKERS
OF THE CHORNOBYL ACCIDENT AND THEIR SURVIVAL
D. Bazyka*,1, N. Gudzenko1, I. Dyagil1, N. Trotsiuk1, E. Gorokh2, Z. Fedorenko2, V. Chumak1,
E. Bakhanova1, I. Ilienko1, A. Romanenko1
1National Research Center for Radiation Medicine of the National Academy of Medical Sciences
of Ukraine, Kyiv 04050, Ukraine
2National Cancer Institute, Kyiv 03022, Ukraine
The study presents the updated data on the multiple myeloma (MM) incidence in Ukrainian cleanup workers after the Chornobyl
accident and their survival. The epidemiological analysis is based on the extended follow-up period to identify new MM cases for
higher statistical power and to collect additional data on the disease course and outcome for the survival analysis. The objective
of the study was to analyze the MM incidence and survival in Chornobyl cleanup workers in 1996–2013 in comparison with the
national MM statistical data. Materials and Methods: A study cohort consisted of 152,520 male cleanup workers resided in one
of 6 regions of Ukraine or Kyiv city and registered in the Ukrainian State Chornobyl Registry (SChR). The Cohort Database was
linked to the Ukrainian National Cancer Registry (NCR) Database to identify MM cases and to analyze MM incidence in 1996–
2013. Standardized incidence ratios (SIR) for MM over the period 1996–2013 were calculated as compared to the general popu-
lation of Ukraine. A 10-year lag period (when incident cases are not considered radiation-related) was applied. One-year and 5-year
cause-specific survival of MM cases were calculated as percentage of those who were alive correspondingly for 1 or 5 years after
diagnosis among overall diagnosed. By the moment, the 5-year survival rate either for the sub-period 2008–2013 or for the whole
study period 1996–2013 cannot be determined. Vital status data were updated according to the recent SChR and NCR informa-
tion. Results: 75 MM cases diagnosed in 1986–2013 were identified in the studied cohort. 69 of them were included to the incidence
analysis considering a 10-year lag period. While the incidence over 15 years after the accident did not differ significantly from the
corresponding rate in general population of Ukraine, a tendency to increase was seen in the period from 16 to 21 years after the
accident, and significantly increased SIR estimate was revealed for 2008–2013 (SIR 1.86, 95% confidence interval (CI) 1.27–2.44).
The highest incidence was detected in 2008–2013 among cohort members diagnosed over the age of 50 years mostly due to the
significant excess among those aged 60–69 (SIR 2.46, 95% CI 1.32–3.59). Survival rates in cleanup workers were shown
to be higher than in the general population of Ukraine (73.9% and up to 65.0%, respectively). Conclusions: SIR for the 2008–
2013 period, 22–27 years after the accident, demonstrated the significant excess of MM incidence among male cleanup workers.
Survival of MM cases is higher in cleanup workers in comparison with that in general population. This article is a part of a Special
Issue entitled “The Chornobyl Nuclear Accident: Thirty Years After”.
Key Words: Chornobyl accident, cleanup workers, multiple myeloma, incidence, survival.
Multiple myeloma �MM� represents a malignancy
from mature B-cell lymphocytes that may appear after
the exposure to ionizing radiation. The effect of ionizing
radiation is still de�ata�le although some evidence was
received from the studies of population groups irradia-
ted due to the accidents� professional or medical needs.
Potential causative role of ionizing radiation in MM in-
duction was shown in the mortality studies of survivors
after A-�om�ing in Japan [�]� although incidence study
among the Life Span Study cohort ��95������� did not
confirm these findings [�]. However� the MM incidence
was higher among nuclear industry workers than in the
general population. The �5-country colla�orative study
of cancer risk among radiation workers reported a�out
a marginally significant association for MM [�]. Also the
study completed �y IARC in �995 among nuclear wor-
kers from facilities in the USA� the UK and Canada found
weak �ut statistically significant association �etween
occupational exposure and the risk of MM �one-sided
p value = �.���; 44 deaths� [4]. А positive association
�etween MM and low level doses of external exposure
increasing with the age at exposure was shown among
nuclear workers at the US �epartment of Energy facili-
ties [5]. MM was in excess in the Hanford Nuclear Res-
ervation cohort [�]. A case-control study of MM risk and
internal uranium dose among workers at the Oak Ridge
Gaseous �iffusion Plant showed weak statistically sig-
nificant association [�]. In the French cohort of nuclear
wor kers an excess of �orderline statistical significance
for MM was o�served [�]. �espite the o�served healthy
worker effect in general for MM there was an indication
of an increasing trend in risk with external dose �p = �.���.
On the other hand� some recent studies in Czech
uranium miners [9] and in patients treated with pelvic ra-
diotherapy [��] have shown no excess of MM. Highly ex-
posed due to treatment were shown to have higher risk
of MM incidence although not significantly. In Ukraine
the MM incidence in ��������� was �.���.� per
������� population� it increased significantly with age
and had non-homogenous time trends. The incidence
of MM was higher in males than in females. First year
mortality in newly diagnosed MM patients in Ukraine
in ��������� decreased ranging from 4�.� to �4.�%
with a su�stantially higher portion of deceased within
Submitted: June 29, 2016.
*Correspondence: E-mail: bazyka@yahoo.com
Abbreviations used: MM — multiple myeloma; NCR — National
Cancer Registry; NRCRM — National Research Center for Radia-
tion Medicine; RBM — red bone marrow; SChR — State Chornobyl
Registry; SIR — standardized incidence ratio.
Exp Oncol ����
��� 4� �������
��� Experimental Oncology ��� �������� ���� ��ecem�er�
� year among males. Correspondingly� �-year survival
increased with time and ranged from 59.� to �5.4% [��].
After the Chorno�yl accident� hundreds of thou-
sands of cleanup workers �predominantly males�
were irradiated while working in the territories around
the nuclear power plant. Hematological malignancies
were among the first expected outcomes in exposed
population that motivated scientific community to initi-
ate widespread investigations.
The study on MM in a range of malignant hemato-
logical disorders in Chorno�yl cleanup workers pro-
vides an opportunity to verify dependencies explored
earlier and to get additional data on MM appearance
after low dose/dose rate radiation exposure.
The o�jective of the study was to analyze standar-
dized incidence ratio �SIR� of MM and survival in a co-
hort of male cleanup workers in �99������.
MATERIALS AND METHODS
The study cohort was assem�led �asing on the State
Chorno�yl Registry �SChR� and consisted of �5��5�� male
cleanup workers resided � o�lasts of Ukraine �Cherkassy�
Chernihiv� �nipropetrovsk� �onetsk� Kharkiv� Kyiv� and
Kyiv city. Periodically updated personal data �demo-
graphic information and results of annual health checks�
were transferred from the SChR �ata�ase to the cohort
file at the National Research Center for Radiation Medi-
cine �NRCRM� [��� ��]. The cohort includes males who
were exposed in young or middle age predominantly.
A�out ��% were younger than 4� at first exposure �mean
age �4.5 years� �Ta�le ��.
Table 1. Main characteristics of the study cohort of Ukrainian liquidators
and MM cases identified in this cohort in 1996–2013
Age group,
years
Cohort under follow up,
number of subjects, n (%)
MM cases,
number of subjects, n (%)
Attained age
at registration
in the SChR
Age at first
exposure
Attained age
at registration
in the SChR
Age at first
exposure
< 30 21,226 (13.9) 43,358 (28.4) 5 (7.2) 8 (11.6)
30–39 55,448 (36.4) 62,866 (41.2) 20 (29.0) 32 (46.4)
40–49 42,220 (27.7) 25,238 (16.5) 21 (30.4) 21 (30.4)
50–59 21,953 (14.4) 8381 (5.5) 16 (23.2) 3 (4.3)
60–69 9666 (6.3) 773 (0.5) 7 (10.1) 0
≥ 70 1578 (1.0) 0 0 0
Unknown 429 (0.3) 11,899 (7.8) 0 5 (7.2)
Total 152,520 (100) 152,520 (100) 69 (100) 69 (100)
Mean age,
years (± SD)
41.1 (± 11.1) 34.5 (± 8.8) 45.1 (± 10.9) 38.2 (± 0.9)
The study on MM among cleanup workers was initi-
ated within the framework of the joint U.S.-Ukrainian
study on leukemia and other hematological disorders.
At that time� data on patients with MM diagnosed in the
period �9������� were identified �y search in local
and state hematological departments. Further inves-
tigation was carried out �y the NRCRM group. The
Cohort �ata�ase was linked to the Ukrainian National
Cancer Registry �NCR� �ata�ase to identify MM cases
diagnosed in the cohort in ���������.
Cases diagnosed �efore ���� were reviewed �y the
International �iagnostic review panel and classified
using the International Staging System [��]. For cases
diagnosed in ��������� a validation procedure was
performed using the medical records and pathology
information o�tained from the NCR and reviewed
�y the NRCRM experts.
Individual doses to red �one marrow �RBM� due
to su�ject’s external exposure were reconstructed
retrospectively using a time-and-motion RA�RUE
method� which was developed for studies of the Chor-
no�yl accident consequences �y the international
group of experts [�4]. We ta�ulated the demographic
characteristics of verified MM cases and calculated
crude rates as well as SIR for cleanup workers using
the Ukrainian population statistics. We calculated
trends in �- and 5-year survival for MM over the period
from �99� to ����. To analyze at least �-year survival
of patients we controlled the vital status of all identified
cases until and over ���4.
Flow cytometry analysis was performed using �-la-
ser flow cytometer FACScali�ur �Becton �ickinson�
USA� equipped with two lasers with excitation waves
length of 4�� and ��5 nm. Whole �lood and �one
marrow samples were stained using a standard B� pro-
cedure with com�inations of monoclonal anti�odies
in two- and three-color assay. Panel of monoclonal
anti�odies �all from Becton �ickinson� included: anti-
C�45/�4; anti-C�5/��/�9; anti-C���/�; anti-C���/
HLA�R; anti-C��/4/�; anti-C�45/5�/���; anti-
C��5/��; anti-C��9/��/��; anti-C��4/��. At �atch
analysis the main B-cell su�sets were identified using
the standard operational procedure. �uring �atch
analysis three-color staining C�45/SSC graphs were
used for setting lymphoid cell discrimination and at the
next stage C�5�+���+ cell su�set was identified at two-
dimensional graph of C�45+SSC low gated cells.
RESULTS
�5 cases of MM were identified in the studied cohort
in �9�������. � cases diagnosed in �9����995 were not
included into analysis according to the applied ��-year
lag period. SIR were calculated for �9 MM cases identi-
fied in the cohort during the follow-up period �99������.
The demographic characteristics of these cases are
given in Ta�le � together with the characteristics of the
cohort. Mean attained age of the identified MM cases
was 45.�� and it was 4�.� for cleanup workers at whole�
a�out half of them were younger than 4� at time of regis-
tration in SChR. MM cases in average did not differ from
the whole cohort mem�ers in age they started participa-
ting in cleanup �mean age at first exposure was ��.� and
�4.5 years� correspondingly�. Su�jects first exposed
�efore age 4� comprise respectively 5�.� and �9.9%.
All �ut one cases were aged over 4� at the time of their
diagnosis� median age at diagnosis was 5� years.
Clinical data for each case and �iological material
samples �peripheral �lood� �one marrow or trepano-
�iopsy� for most of them were reviewed to confirm
or clarify the diagnosis. Each of the identified cases
diagnosed in �99������ has undergone the diagnosis
verification procedure �y the independent �iagnostic
Review Panel of qualified hematologists and hemato-
pathologists from the USA� France� the United Kingdom
and Ukraine. The Panel’s consensus opinion was the
Experimental Oncology ��� �������� ���� ��ecem�er���� �������� ���� ��ecem�er� ��ecem�er� ��9
Review conclusion [�5]. High quality of MM diagnostics
was recognized due to the high percentage of morpho-
logically confirmed MM cases in general population
of Ukraine �9�%� and the confirmation rate achieved
after the international diagnostic review of MM cases
diagnosed in �99������� when 5 diagnoses of �5 re-
viewed cases were not confirmed� � of them just due
to the lack of diagnostic material samples.
According to the performed analysis� MM incidence
rate in the studied cohort of cleanup workers did not differ
significantly from the corresponding rate in the general
population of Ukraine for the period from �� to �5 years
after the accident; a tendency to increase was demon-
strated in the period from �� to �� years after the ac-
cident� and significantly increased rates were revealed
in ��������� �SIR �.��� 95% confidence interval �CI�
�.����.44�� resulting in the excess during the whole
study period �Ta�le ��. Persons diagnosed over the age
of 5� were more vulnera�le mostly due to the significant
excess in ��������� among those aged ����9 �SIR
�.4�� 95% CI �.����.59�. Other su�groups of those older
than 5� at diagnosis �5��59� and ≥ ��� haven’t shown any
significant excess either during the whole study period
or �y su�-periods.
Table 2. SIR for MM in the cohort of male cleanup workers in 1996–2013
Period of obser-
vation
Person-
years
of obser-
vation
Number
of cases
Crude
rate
per
105
SIR (95% CI)ob-
served
expec-
ted
1996–2001 823,198 13 13.2 1.58 0.98 (0.45–1.52)
2002–2007 707,428 17 15.7 2.4 1.08 (0.57–1.60)
2008–2013 593,309 39 21.0 6.6 1.86 (1.27–2.44)
1996–2013 2,123,934 69 49.9 3.24 1.38 (1.06–1.71)
Age at diagnosis
< 50 983,091 10 9.7 1.02 1.03 (0.39–1.67)
≥ 50 1,140,843 59 37.9 5.17 1.56 (1.16–1.95)
The RBM doses due to external irradiation were re-
constructed for �� of �9 identified MM cases. �ose values
were in the range from �.� to ��9�.� mGy. In � ��5.�%�
cases the RBM doses were higher than ��� mGy. We plan
to continue dose reconstruction for identified MM cases
and for corresponding controls selected within the study
cohort to analyze possi�le radiation risks.
As to identified cases �Ta�le ��� �-year survival indices
were shown to �e higher than for those diagnosed in the
general population of Ukraine ���.9% and up to �5%
correspondingly� [��]. Greater survival in cleanup wor-
kers may result from �etter medical service in population
groups affected �y the Chorno�yl accident comparing
with the general population. One-year survival among the
cases diagnosed �efore age 5� was expectedly higher
than in older cases �ut not significantly.
By the end of o�servation period 4� ���.9%� pa-
tients were deceased �Ta�le ��. Analysis of the clinical
course of the cases showed that the majority of the
MM diagnoses were esta�lished at late stages of di-
sease with an involvement of the �one system� kidney�
hemorrhagic syndrome due to the high level of a�nor-
mal proteins in the �lood and urine. All of these patients
were diagnosed in �99������. Treatment strategies
included monochemotherapy and radiotherapy.
Table 3. 1-year and 5-year survival of MM cases by sub-period of obser-
vation and age at diagnosis
Period of obser-
vation (cases di-
agnosis)
Number
of cases
(cases de-
ceased over
2013, %)
Mean age
(median
age) at di-
agnosis,
years
1-year sur-
vival, n (%)
5-year sur-
vival, n (%)
1996–2001 13 (92.3) 54 (57) 9 (69.2) 2 (15.4)
2002–2007 17 (76.5) 54 (53) 14 (82.4) 6 (35.3)
2008–2013 39 (43.6) 62 (62) 28 (71.8) n.d.*
1996–2013 69 (60.9) 58 (58) 51 (73.9) n.d.
Age at diagnosis
< 50 10 (70.0) 45 (46) 8 (80) n.d.
≥ 50 59 (59.3) 61 (60) 44 (74.6) n.d.
Note: *n.d. — non-determinable.
In the later period from ���� to ����� case diagnostics
improved and patients were diagnosed at earlier stages
of the disease. Proper diagnosis of solitary myeloma and
MM without marked changes in �one tissue �ecame
possi�le. MM diagnosis in � cases �efore ���� was
esta�lished using classical clinical criteria �y the Inter-
national Review Group. A certain progress was achieved
after implementation of flow cytometry. To investigate
�one marrow and peripheral �lood clonal proliferative
plasma cell pool the immunophenotyping was performed
for �� cases. Typical MM cells were C���+ and C�5�+
with low expression of B-lineage antigens C��9� C����
C���� C��� and early antigens like C���. MM phenotype
has to �e differentiated with the changes in monoclonal
gammopathy of undetermined significance and NK-cell
leukemia. For such cases C�5�/45/��� staining was
implemented resulting in an increased quality of diagnos-
tics �Figure�. Treatment of MM �ecame more intensive with
the use of modern protocols and su�sequent autologous
stem cell transplantation in patients younger than �5 years.
This approach can significantly improve the effective-
ness of treatment and patients’ quality of life. Elongation
of MM cases survival is also associated with the advent
of effective therapeutic drugs for this group of patients.
DISCUSSION
This study demonstrates increased incidence rates
of MM in a cohort of Chorno�yl cleanup workers in a period
up to �� years after the accident as compared to the gene-
ral population of Ukraine. Strength of this study is in the use
of updated cohort ensuring statistical significance of the
results [��]. These data are in conformity with previously
o�tained data [��]� indicating an MM incidence increase
with time since exposure. Our results are consistent
in gene ral with conclusions o�tained in other long-term
studies in nuclear workers� i.e. in a mortality study per-
formed in a pooled cohort of ��9��95 U.S. nuclear work-
ers at five nuclear facilities �Hanford site� Idaho National
La�oratory� Oak Ridge National La�oratory� Savannah
River site and at the Portsmouth Naval Shipyard�. The
cohort was followed at the start of the workers �eginning
their radiation work �at earliest� �etween �944 and �95��
through ���5. The dose dependent excess relative risk
was shown for MM �ERR per �� mSv was �.9% �95%
CI �.���9.5%� [��]. Unlike this study our aim was to reveal
just incidence rates and survival during the study period.
At the same time� planned reconstruction of RBM doses
��� Experimental Oncology ��� �������� ���� ��ecem�er�
for identified cases and matched controls will provide the
possi�ility of dose-dependent risk estimates.
100
100
101
101
102
FL1-H
Control
FL
2-
H
102
103
103
104
104
100
100
101
101
102
FL1-H
6.2% CD138+CD56+ 22.9%
0.5%70.4%
FL
2-
H
102
103
103
104
104
b
a
Figure. Expression of C���� and C�5� on MM cells: a� control
staining; b� staining with C����-FITC and C�5�-PE
The uncertainties in our study as well as in other
long-term studies are related to quality of diagnostic
approaches used for case validation which are impro-
ving with time. Our group tried to reduce the influence
of such factors at the first stage of the study ��9���
������ when the NCR data were not availa�le� �y invi-
ting the International Review Group for case diagnostic
verification. Later cases were diagnosed �y the up-
to-date approach that ena�led one to differentiate
�enign monoclonal B-lymphocytosis� unspecified
monoclonal gammopathies� and other mature B-cell
disorders. Such an approach is recommended �y other
researchers [�����]. Hence� cases registered in the
NCR were diagnosed with the up-to-date approaches.
However� influence of differences in diagnostics quality
on MM incidence in exposed and not-exposed groups
remains unclear. This study hasn’t revealed significant
differences in the MM natural course influencing timely
diagnosis.
This study also demonstrated �etter survival rates
for cleanup workers in comparison with the general
population of Ukraine. This difference could �e related
to the �etter health care and treatment opportunities
in radiation exposed su�jects.
Our study provides the informative �ase for the
consequent case-control study on dose dependent
MM risk estimates. Next steps in our research will
�e the following: incidence density sampling of the
controls in the study cohort accounting for the attained
age and region of residency; dose reconstruction for
all identified cases and corresponding controls with
RA�RUE method; applying the statistical models for
MM risk evaluation.
CONCLUSIONS
The MM incidence in the male Chorno�yl cleanup
workers in �99������ significantly exceeds the corres-
ponding rate in the general population of Ukraine with
the highest SIR for the latest period of o�servation�
���������. O�served MM incidence excess was due
to the excess in those older than 5� at diagnosis mostly
due to patients aged ����9. Survival of MM patients
in the male cleanup workers cohort exceeds that in the
general population of the corresponding gender and
age. It tends to �e higher in the youngest men and
decreases with increasing age. A case-control study
needs to �e carried out to confirm dependencies
in MM incidence on radiation dose if exist.
ACKNOWLEDGEMENTS
This research was partly supported �y the Intra-
mural Research Program of the U.S. National Cancer
Institute. Authors are greatly thankful to International
Hematology Review Panel mem�ers — �r. B. Bain �Im-
perial College School of Medicine� Saint Mary’s Hos-
pital� UK�� Prof. S. Gajdukova �Kyiv Academy of Post-
Graduate Medical Training� Ukraine�� Prof. �. Gluzman
�R.E. Kavetsky Institute of Experimental Pathology�
Oncology and Radio�iology of the NAS of Ukraine�
Ukraine�� �r. P. McPhedran �Yale New Haven Hospital�
USA�� �r. L.-A. Peterson �Fein�erg Medical School
of Northwestern University� USA� for their expertise
and invalua�le advice. We would like to acknowledge
the significant efforts of �rs. S.C. Finch and R. Reiss
for their preliminary expertise of diagnostic material
and preparing the International �iagnostic Review.
We are especially grateful to the local hematology staff
for their diligent work of preparing clinical records and
�iological materials for case ascertainment as well
as the local technical staff for their enormous work
on tracing and contacting cases.
REFERENCES
1. Pierce DA, Shimizu Y, Preston DL, et al. Studies of the
mortality of atomic bomb survivors. �e�ort 1�� �art �. �a���e�ort 1�� �art �. �a��
cer: 1950–1990. �adiat �es 1996; 146: 1–�7.
�. Hsu WL, Preston DL, Soda M, et al. The i�cide�ce
of leukemia� lym�homa a�d multi�le myeloma amo�g atomic
bomb survivors: 1950–�001. �adiat �es �013; 179: 361–8�.
3. Cardis E, Vrijheid M, Blettner M, et al. The 15�cou�try
collaborative study of ca�cer risk amo�g radiatio� workers
i� the �uclear i�dustry: estimates of radiatio��related ca�cer
risks. �adiat �es �007; 167: 396–416.
4. Cardis E, Gilbert ES, Carpenter L, et al. Effects of low
doses a�d low dose rates of exter�al io�izi�g radiatio�: ca�cer
mortality amo�g �uclear i�dustry workers i� three cou�tries.
�adiat �es 1995; 142: 117–3�.
5. Wing S, Richardson D, Wolf S, et al. A case co�trol study
of multi�le myeloma at four �uclear facilities. A�� E�idemiol
�000; 10: 144–53.
6. Dement JM, Ringen K, Welch LS, et al. Mortality of older
co�structio� a�d craft workers em�loyed at De�artme�t of E��
ergy (DOE) �uclear sites. Am J ��d Med �009; 52: 671–8�.
Experimental Oncology ��� �������� ���� ��ecem�er���� �������� ���� ��ecem�er� ��ecem�er� ���
7. Yiin JH, Anderson JL, Daniels RD, et al. A �ested case�
co�trol study of multi�le myeloma risk a�d ura�ium ex�osure
amo�g workers at the Oak �idge Gaseous Diffusio� �la�t.
�adiat �es �009; 171: 637–45.
8. Telle-Lamberton M, Samson E, Caër S, et al. Exter�al
radiatio� ex�osure a�d mortality i� a cohort of Fre�ch �uclear
workers. Occu� E�viro� Med �007; 64: 694–700.
9. Rericha V, Kulich M, Rericha R, et al. ��cide�ce of leu�
kemia� lym�homa� a�d multi�le myeloma i� �zech ura�ium
mi�ers: a case — cohort study. E�viro� Health �ers�ect �006;
114: 818–��.
10. Wright JD, St Clair CM, Deutsch I, et al. �elvic ra�
diothera�y a�d the risk of seco�dary leukemia a�d multi�le
myeloma. �a�cer �010; 116: �486–9�.
11. Natio�al �a�cer �egistry of Ukrai�e [home�age o� the ��ter�
�et]. Kyiv: Natio�al �a�cer �egistry of Ukrai�e [cited �016 Ju� �9].
Available from: htt�://www.�cru.i�f.ua/�ublicatio�s/i�dex.htm.
1�. Romanenko A, Bebeshko V, Hatch M, et al. The
Ukrai�ia��America� study of leukemia a�d related disorders
amo�g �hor�obyl clea�u� workers from Ukrai�e: �. Study
methods. �adiat �es �008; 170: 691–7.
13. Zablotska LB, Bazyka D, Lubin JH, et al. �adiatio�
a�d the risk of chro�ic lym�hocytic a�d other leukemias
amo�g �hor�obyl clea�u� workers. E�viro� Health �ers�ect
�013; 121: 59–65.
14. Kryuchkov V, Chumak V, Maceika E, et al. �AD�UE
method for reco�structio� of exter�al �hoto� doses for �her�
�obyl liquidators i� e�idemiological studies. Health �hys
�009; 97: �75–98.
15. Dyagil I, Adam M, Beebe GW, et al. Histologic veri�
ficatio� of leukemia� myelodys�lasia� a�d multi�le myeloma
diag�oses i� �atie�ts i� Ukrai�e� 1987–1998. ��t J Hematol
�00�; 76: 55–60.
16. Bazyka DA, Gudzenko NA, Dyagil IS, et al. Multi�le
myeloma amo�g �hor�obyl accide�t clea�u� workers — state
a�d �ers�ectives of a�alytical study. �robl �adiac Med �adio�
biol �013; (18): 169–7�.
17. Schubauer-Berigan MK, Daniels RD, Bertke SJ, et al.
�a�cer mortality through �005 amo�g a �ooled cohort of U.S.
�uclear workers ex�osed to exter�al io�izi�g radiatio�. �adiat
�es �015; 183: 6�0–31.
18. Junxun L, Juan L, Xiuzhen T, et al. �om�ari�g five
diag�ostic criteria for multi�le myeloma: a retros�ective study
of ��7 cases. Tumori �014; 100: �07–13.
19. Alley CL, Wang E, Dunphy CH, et al. Diag�ostic a�d
cli�ical co�sideratio�s i� co�comita�t bo�e marrow i�volve�
me�t by �lasma cell myeloma a�d chro�ic lym�hocytic leuke�
mia/mo�oclo�al B�cell lym�hocytosis: a series of 15 cases a�d
review of literature. Arch �athol Lab Med �013; 137: 503–17.
�0. Matsue K, Matsue Y, Kumata K et al. Qua�tificatio�
of bo�e marrow �lasma cell i�filtratio� i� multi�le myeloma: use�
ful�ess of bo�e marrow as�irate clot with �D138 immu�ohisto�
chemistry. Hematol O�col �016; doi: 10.100�/ho�.�300 [E�ub
ahead of �ri�t].
Copyright © Experimental Oncology, 2016
|