Vo
lu
m
e
5,
M
ay
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
MANAGEMENT OF PATIENTS WITH MULTIPLE MYELOMA FOLLOWING
AUTOLOGOUS BONE MARROW TRANSPLANTATION
Nuriddin Najmiddinovich Temirov
Head of the Hematology Centre,
Samarkand Regional Multidisciplinary Medical Centre
Kadir Ergashevich Shomurodov
Hematologist, Hematology Centre,
Samarkand Regional Multidisciplinary Medical Centre
Dilafruz Abdikhalimovna Amerova
Assistant teachet of the Department of Hematology,
Samarkand State Medical University
Abstract
. Autologous bone marrow transplantation (ABMT) remains a fundamental
component of treatment for patients with multiple myeloma (MM), offering deep remission
and prolonged survival when combined with modern therapeutic strategies. This study
evaluates the clinical outcomes, complications, and effectiveness of post-transplant
maintenance therapy in MM patients treated at a regional haematology centre in Uzbekistan.
A total of 64 patients who underwent high-dose melphalan conditioning followed by ABMT
were included. The majority achieved deep responses, with complete response (CR) in
62.5% and very good partial response (VGPR) in 21.9%. Lenalidomide-based maintenance
therapy significantly improved 2-year progression-free survival (72% vs 45%, p = 0.038).
Common post-transplant complications included infections (43.8%) and manageable non-
infectious events such as mucositis and thrombocytopenia. No early transplant-related
mortality occurred. These findings confirm the safety and efficacy of ABMT in MM and
emphasise the importance of structured post-transplant management, including maintenance
therapy and supportive care, to optimise long-term outcomes in resource-limited settings.
Keywords:
Multiple myeloma, autologous transplantation, bone marrow transplant,
maintenance therapy, lenalidomide, transplant complications, survival, Uzbekistan.
Introduction
Multiple myeloma (MM) is a clonal plasma cell malignancy that accounts for approximately
10–15% of haematologic cancers. It is characterised by uncontrolled proliferation of plasma
cells in the bone marrow, leading to excessive monoclonal immunoglobulin production and
subsequent organ damage, commonly referred to as the CRAB criteria (hyperCalcaemia,
Renal insufficiency, Anaemia, and Bone lesions). Despite being considered incurable, the
advent of novel therapies and the integration of autologous haematopoietic stem cell
transplantation (AHSCT)—commonly known as autologous bone marrow transplantation
(ABMT)—have significantly improved patient outcomes, transforming multiple myeloma
into a chronic, manageable disease for many patients.
Vo
lu
m
e
5,
M
ay
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
Autologous transplantation has been the standard of care for transplant-eligible patients
under 70 years of age with good performance status. It is typically performed after 3–6
cycles of induction chemotherapy using modern regimens containing bortezomib,
lenalidomide, or thalidomide, followed by high-dose melphalan conditioning and reinfusion
of the patient’s previously collected stem cells. This approach allows for deep cytoreduction
and achievement of minimal residual disease (MRD), which is now widely recognised as a
major prognostic factor in long-term disease control.
The post-transplant period, however, represents a critical phase in the treatment trajectory.
Despite successful stem cell engraftment and initial remission, patients are at considerable
risk of relapse due to the persistence of residual malignant plasma cells. Without
maintenance therapy, median progression-free survival (PFS) after ABMT is typically
limited to 24–36 months. Hence, maintenance strategies—most commonly with
lenalidomide—are routinely employed to extend remission, delay relapse, and potentially
improve overall survival. However, maintenance therapy must be balanced with
considerations of toxicity, financial burden, and patient-specific risk factors such as
cytogenetics and comorbidities.
Another key challenge after ABMT is immune suppression. High-dose chemotherapy
induces profound lymphopenia and delays immune reconstitution, predisposing patients to
infections including bacterial pneumonias, herpes zoster reactivation, and fungal
complications. In regions with limited access to prophylactic antimicrobial agents and
supportive care, such infections can significantly impact survival and quality of life.
Furthermore, prolonged use of steroids, bisphosphonates, and immunomodulatory drugs
contributes to additional risks including osteonecrosis, gastrointestinal complications,
cytopenias, and thromboembolic events.
In addition, comprehensive post-transplant management must address other long-term
complications such as therapy-related myelodysplasia or secondary acute leukaemia, renal
dysfunction progression, persistent bone disease, neuropathy, and psychological distress.
These issues require an interdisciplinary and patient-centred approach, incorporating regular
clinical monitoring, bone marrow assessments, imaging, laboratory surveillance, and
appropriate psychosocial support.
Globally, the role of ABMT continues to evolve with the introduction of next-generation
therapies such as CAR-T cells, bispecific antibodies, and monoclonal antidiv-based
induction regimens. Nevertheless, in resource-constrained settings like Uzbekistan, ABMT
remains a highly valuable therapeutic intervention. In recent years, significant progress has
been made in establishing transplant infrastructure and training specialists. However,
structured post-transplant monitoring and data collection remain limited, which hinders
evidence-based refinement of care pathways.
This study therefore aims to evaluate the outcomes, complications, and effectiveness of post-
transplant management strategies in patients with multiple myeloma treated with autologous
bone marrow transplantation at the Samarkand Regional Haematology Centre. By analysing
clinical parameters, relapse rates, complications, infection profiles, and responses to
maintenance therapies, this study will provide important insights into regional challenges
and help inform national protocols. Ultimately, the findings may contribute to standardising
Vo
lu
m
e
5,
M
ay
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
post-ABMT care and improving survival and quality of life for patients living with multiple
myeloma in Uzbekistan and similar healthcare environments.
Methodology
This retrospective observational study was conducted at the Haematology Centre of the
Samarkand Regional Multidisciplinary Medical Centre between January 2019 and
December 2023. The aim of the study was to assess the clinical outcomes, complications,
and management strategies in patients with multiple myeloma (MM) following autologous
bone marrow transplantation (ABMT). The study focused on evaluating relapse rates, post-
transplant complications (particularly infections and cytopenias), effectiveness of
maintenance therapy, and overall patient survival in a regional outpatient setting.
A total of 64 adult patients with a confirmed diagnosis of multiple myeloma who underwent
ABMT during the study period were included. All patients met the International Myeloma
Working Group (IMWG) criteria for symptomatic MM and were deemed eligible for high-
dose therapy and autologous transplantation following initial induction chemotherapy.
Patients with primary refractory disease, active infections at the time of transplant, or
incomplete follow-up data were excluded from the analysis.
Transplant Protocol
All patients received high-dose melphalan (200 mg/m²) as a conditioning regimen prior to
reinfusion of autologous haematopoietic stem cells, which had been harvested after
induction therapy with bortezomib-based combinations (e.g., VCD – bortezomib,
cyclophosphamide, dexamethasone or VRD – bortezomib, lenalidomide, dexamethasone).
Stem cells were mobilised using granulocyte colony-stimulating factor (G-CSF) with or
without cyclophosphamide. Supportive care included prophylactic antimicrobials, growth
factors, and transfusion support according to institutional protocols.
Post-Transplant Monitoring and Management
Patients were followed for a minimum of 12 months post-transplant. Clinical assessments
were conducted monthly for the first 6 months and every 2–3 months thereafter. Laboratory
tests included complete blood counts, serum protein electrophoresis, serum free light chain
assays, renal function tests, and inflammatory markers. Bone marrow biopsy and imaging
(PET-CT or MRI) were performed as indicated to assess treatment response and disease
progression. Response to treatment was assessed according to IMWG criteria, including
complete response (CR), very good partial response (VGPR), partial response (PR), and
progressive disease (PD). Minimal residual disease (MRD) evaluation was not routinely
performed due to resource limitations. Patients who achieved at least VGPR post-transplant
were offered maintenance therapy with lenalidomide (10 mg/day, 21 days per cycle), or
thalidomide in resource-constrained cases. Those unable to tolerate maintenance due to
toxicity were monitored off therapy.
Complications such as febrile neutropenia, herpes zoster reactivation, bacterial pneumonias,
gastrointestinal toxicities, thromboembolic events, and cytopenias were recorded. Infection
episodes were classified according to severity and need for hospitalisation. Supportive
therapies—including bisphosphonates, erythropoietin, and prophylactic antivirals or
antifungals—were documented.
Statistical Analysis
All collected data were anonymised and entered into a central database. Statistical analysis
was performed using SPSS version 26.0. Descriptive statistics were used to summarise
demographic and clinical data. Kaplan–Meier curves were generated to estimate
progression-free survival (PFS) and overall survival (OS). Differences in outcomes between
Vo
lu
m
e
5,
M
ay
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
subgroups (e.g., maintenance vs no maintenance) were assessed using the log-rank test. A p-
value < 0.05 was considered statistically significant. Ethical approval was obtained from the
Institutional Ethics Committee of Samarkand State Medical University. Informed consent
for treatment and data use was obtained from all patients prior to transplantation.
Results
A total of 64 patients with multiple myeloma (MM) who underwent autologous bone
marrow transplantation (ABMT) at the Samarkand Regional Haematology Centre were
included in the analysis. The median age was 58 years (range: 42–70), with a male-to-female
ratio of 1.2:1. Most patients (87.5%) had IgG-type myeloma, while the remaining had IgA
or light chain-only variants. High-risk cytogenetic abnormalities (such as del(17p) or t(4;14))
were present in 14.1% of patients, based on fluorescence in situ hybridisation (FISH) testing
where available.
Transplant Outcomes
All patients underwent high-dose melphalan conditioning and stem cell reinfusion.
Neutrophil engraftment was achieved at a median of day +11 (range: 9–15), and platelet
engraftment occurred by day +14 (range: 11–21). Early transplant-related mortality was 0%,
indicating a high safety profile of the ABMT procedure in this setting. Following
transplantation, 90.6% of patients (58 out of 64) achieved at least a partial response (PR),
with 62.5% achieving complete response (CR) and 21.9% achieving very good partial
response (VGPR). Six patients (9.4%) had only a minimal response or stable disease.
Response depth was strongly correlated with the quality of the pre-transplant induction
response (p < 0.01). MRD assessment was not performed routinely due to resource
constraints.
Maintenance Therapy and Relapse Rates
Out of 58 patients who achieved VGPR or better, 40 (69%) received lenalidomide-based
maintenance therapy, while 6 received thalidomide due to drug availability. The remaining
12 patients (20.6%) declined or could not tolerate maintenance therapy due to adverse
effects such as cytopenia, fatigue, or thromboembolic complications.
After a median follow-up of 22 months (range: 12–46 months), 13 patients (20.3%)
experienced disease progression. The 2-year progression-free survival (PFS) rate was 72%
in the maintenance group versus 45% in those without maintenance (p = 0.038). The overall
survival (OS) rate at 2 years was 85%, with only 6 recorded deaths—3 due to disease
progression and 3 due to infectious complications during relapse treatment.
Post-Transplant Complications
Infectious complications were reported in 28 patients (43.8%). The most common were
bacterial infections (particularly pneumonia and urinary tract infections), followed by herpes
zoster reactivation (7 cases) and one case of probable invasive aspergillosis. Most infections
were managed with outpatient antimicrobial therapy, but 9 patients required hospitalisation.
No deaths were attributed to early infectious complications.
Vo
lu
m
e
5,
M
ay
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
Non-infectious complications included:
Grade II–III thrombocytopenia lasting beyond day +30 in 18.7% of patients
Peripheral neuropathy (mostly due to thalidomide) in 5 patients
One case of venous thromboembolism (VTE) despite prophylaxis
Gastrointestinal toxicity (nausea, diarrhoea, mucositis) in 32.8% of patients, all self-
limiting
Bone disease was monitored in all patients. Monthly bisphosphonate therapy (zoledronic
acid) was administered to 87.5% of the cohort. No new skeletal-related events were reported
during the follow-up period.
Statistical Findings
Patients who achieved CR post-transplant and received lenalidomide maintenance had
significantly longer PFS compared to those with PR or no maintenance (p < 0.05). High-risk
cytogenetics were associated with shorter time to relapse, although this did not reach
statistical significance (p = 0.08), likely due to the limited number of high-risk patients in
the sample.
In summary, ABMT was safe and effective for multiple myeloma patients in this regional
setting, with high response rates and low transplant-related mortality. Maintenance therapy
with lenalidomide significantly prolonged PFS. Infectious complications were frequent but
mostly manageable. These findings highlight the importance of structured post-transplant
care, including maintenance, infection monitoring, and bone support, to improve outcomes
in real-world clinical practice.
Discussion
The findings of this study confirm the clinical efficacy and safety of autologous bone
marrow transplantation (ABMT) in patients with multiple myeloma (MM), reflecting
outcomes comparable to international benchmarks despite the resource-constrained setting.
High overall response rates, low transplant-related mortality, and acceptable complication
profiles demonstrate the viability of ABMT as a standard consolidation therapy for
transplant-eligible MM patients in Uzbekistan.
A key outcome of this study is the post-transplant response profile, with 62.5% of patients
achieving complete response (CR) and an additional 21.9% reaching very good partial
response (VGPR). These rates are consistent with major studies such as IFM 2009 and
CALGB 100104, which support the use of high-dose melphalan followed by ABMT to
achieve deep, durable remissions. Moreover, the absence of early transplant-related deaths,
alongside timely engraftment, suggests that current transplantation protocols are both
clinically sound and well-tolerated by the local patient population.
Another significant observation is the impact of post-transplant maintenance therapy on
disease control. Patients who received lenalidomide maintenance showed a substantially
higher 2-year progression-free survival (PFS) compared to those who did not (72% vs 45%,
p = 0.038), confirming findings from large trials such as the Myeloma XI and IFM 2005-02
Vo
lu
m
e
5,
M
ay
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
studies. Although maintenance therapy is associated with certain side effects, its benefits in
prolonging remission and delaying relapse clearly outweigh its risks when appropriately
monitored. Thalidomide, though used in a limited number of patients due to resource
limitations, remains a viable alternative in low-income settings despite its inferior side effect
profile.
The incidence of infections (43.8%) post-transplant, including herpes zoster reactivation and
bacterial pneumonias, highlights the need for continued infection prophylaxis and early
detection strategies. While most infections were manageable on an outpatient basis,
approximately 14% required hospitalisation. This reinforces the importance of structured
outpatient follow-up, vaccination protocols, and rapid response systems to mitigate
infection-related morbidity in immunocompromised patients.
Non-infectious complications such as persistent thrombocytopenia, mucositis, and
neuropathy were observed but largely manageable. Notably, long-term bone support with
bisphosphonates prevented further skeletal-related events, underscoring the importance of
comprehensive supportive care in the post-transplant setting.
The relatively low relapse rate observed (20.3%) during the median follow-up period is
promising. However, the presence of high-risk cytogenetics in a subset of patients correlated
with shorter PFS, suggesting a need for future incorporation of risk-adapted strategies, such
as tandem transplantation or early integration of novel agents like monoclonal antibodies or
CAR-T cells. Although MRD monitoring was not feasible in this cohort, its adoption could
significantly enhance response evaluation and guide post-transplant interventions.
Importantly, the findings of this study have practical implications for clinical practice in
Uzbekistan and similar healthcare systems. With increasing access to transplantation
services, there is a pressing need to develop standardised post-ABMT care protocols that
include maintenance therapy, infection prophylaxis, psychosocial support, and timely
laboratory and imaging surveillance. Investment in diagnostic infrastructure, particularly for
MRD assessment and cytogenetic profiling, would further enable precision-guided
management.
In conclusion, ABMT remains a cornerstone in the treatment of multiple myeloma in
transplant-eligible patients. When coupled with effective post-transplant maintenance and
supportive care, it offers durable disease control and improved survival. This study provides
strong regional evidence supporting the continued use and refinement of ABMT in
Uzbekistan and offers a foundation for further prospective, multicentre research to optimise
MM management.
REFERENCES:
1.
Attal, M., Lauwers-Cances, V., Marit, G., et al. (2017). Lenalidomide maintenance
after stem-cell transplantation for multiple myeloma.
New England Journal of Medicine
,
376(26), 2413–2422.
https://doi.org/10.1056/NEJMoa1611750
2.
McCarthy, P. L., Owzar, K., Hofmeister, C. C., et al. (2012). Lenalidomide after
stem-cell transplantation for multiple myeloma.
New England Journal of Medicine
, 366(19),
1770–1781.
Vo
lu
m
e
5,
M
ay
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
3.
Kumar, S. K., Callander, N. S., Baljevic, M., et al. (2021). NCCN Clinical Practice
Guidelines in Oncology: Multiple Myeloma.
Journal of the National Comprehensive Cancer
Network
, 19(10), 1223–1261.
https://doi.org/10.6004/jnccn.2021.0057
4.
Palumbo, A., Avet-Loiseau, H., Oliva, S., et al. (2015). Revised International
Staging System for multiple myeloma: A report from IMWG.
Journal of Clinical Oncology
,
33(26), 2863–2869.
https://doi.org/10.1200/JCO.2015.61.2267
5.
Dimopoulos, M. A., Mateos, M. V., Cavo, M., et al. (2021). The role of maintenance
therapy in multiple myeloma: Current approaches and future directions.
Blood Cancer
Journal
, 11(4), 79.
https://doi.org/10.1038/s41408-021-00453-0
6.
Sonneveld, P., Avet-Loiseau, H., Lonial, S., et al. (2016). Treatment of multiple
myeloma with high-risk cytogenetics: A consensus of the International Myeloma Working
Group.
Blood
, 127(24), 2955–2962.
https://doi.org/10.1182/blood-2016-01-693961
7.
Мадашева, А. Г., & Жураева, М. З. (2019). Биохимические показатели и
комплексное лечение больных псориазом с лечебным плазмаферезом. Достижения
науки и образования, (10 (51)), 78-82.
8.
Ruziboeva, O. N., Abdiev, K. M., Madasheva, A. G., & Mamatkulova, F. K. (2021).
Modern Methods Of Treatment Of Hemostasis Disorders In Patients With Rheumatoid
Arthritis. Ученый XXI века, 8.
9.
Мадашева, А. Г., Дадажанов, У. Д., Абдиев, К. М., Маматкулова, Ф. Х., &
Махмудова, А. Д. (2019). Динамика электронейромиографических показателей и
эффективность электрической стимуляции мышц у больных гемофилией с
мышечными атрофиями. Достижения науки и образования, (10 (51)), 26-30.
10.
Мадашева, А. Г. (2022). Клинико-неврологические изменения у больных
гемофилией с мышечными патологиями. Science and Education, 3(12), 175-181.
11.
Madasheva, A. G., Yusupova, D. M., & Abdullaeva, A. A. EARLY DIAGNOSIS
OF HEMOPHILIA A IN A FAMILY POLYCLINIC AND THE ORGANIZATION OF
MEDICAL CARE. УЧЕНЫЙ XXI ВЕКА, 37.
12.
Turdiyev, Q., Maxmonov, L., Xaqberdiyev, Z., & Madasheva, A. (2025).
FEATURES OF MAINTAINING RENAL FAILURE IN PATIENTS WITH DIABETES
MELLITUS ON GEODIALYSIS. International Journal of Artificial Intelligence, 1(1),
1481-1486.
13.
Мадашева, А. Г., Бергер, И. В., Махмудова, А. Д., Абдиев, К. М., & Амерова, Д.
A. (2025). Самаркандский государственный медицинский университет, Самарканд,
Узбекистан
2
Республиканский
специализированный
научно-практический
медицинский центр гематологии, Ташкент, Узбекистан. Laboratory Diagnostics Eastern
Europe, 87.
14.
Бергер, И. В., Махмудова, А. Д., Мадашева, А. Г., & Ходжаева, Н. Н. (2023).
ПОЛИМОРФИЗМ
ПРОВОСПАЛИТЕЛЬНЫХ
ЦИТОКИНОВ
В
ГЕНЕЗЕ
ТРОМБООБРАЗОВАНИЯ ПРИ ТРОМБОФИЛИИ И АФС. Журнал гуманитарных и
естественных наук, (5), 43-46.
