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Splenomegaly
resulting from either malignant or benign etiology is usually fraught with
symptoms. Many of the symptoms are attributed to variable cytopenias
encountered in individual scenario which necessitate some form of treatment to
control splenic enlargement. Radiotherapy
is an old and proven modality for management of symptomatic splenomegaly. The
trends and patterns of different corpuscular parameters of blood following
splenic irradiation though intriguing is sparse in published literature. In
this case report we have plotted and analyzed the values of hemoglobin [Hb],
Total Leukocyte Count [TLC], Absolute Neutrophil Count [ANC] and Platelet Count
during a protracted course of radiotherapy in a young female with multiple
co-morbidities for symptomatic splenomegaly to prove the safety as well as to
identify the trend and pattern of changes in hematological parameters.
Keywords:Splenomegaly, Radiotherapy, Hemoglobin, TLC, ANC, Platelets
INTRODUCTION
CASE REPORT
Young female of age 32 years with known co-morbidity of rheumatic heart disease (post 10 years of Penicillin prophylaxis) and hypothyroidism (on regular medication, Thyroid Function Tests within normal limits) was evaluated for chronic left upper abdominal pain, heaviness and malaise. Clinical examination revealed a palpable tender splenomegaly approximate 12 cm below left costal margin in midclavicular line without palpable liver/ raised JVP. Abdomen ultrasonography suggested chronic liver disease [CLD] with portal hypertension [PH] and splenomegaly which also was confirmed with contrast enhanced computed tomography of abdomen. Blood count revealed a picture of anemia, leucopenia, neutropenia as well as thrombocytopenia. Peripheral smear commented the anemia as normocytic and normochromic while aspiration cytology and biopsy found bone marrow to be normocellular. A diagnosis of CLD with Portal Hypertension and secondary splenomegaly was made. Splenectomy was disfavored owing to co-morbidities; instead management with irradiation in palliative intent was framed.
Patient was simulated in supine position immobilized with thermoplastic
cast and non-contrast computed tomography slices of 2.5 mm thickness was
obtained from carina upto true pelvis. Images (Figure 1A) were transferred and registered in Monaco treatment
planning system (version5.11), planned using Volumetric Modulated Arc Therapy
[VMAT] (Figure 1B) to a dose of 5Gy
in 10Fractions,0.5 Gy per fraction delivered using 6 megavoltage X-ray by VERSA
HD TM –Elekta twice weekly.
Complete Blood Count (CBC) was recorded before start of radiotherapy.
The values were designated as baseline (0 hours) and subsequently CBC was
repeated at 12 hourly intervals to see changes with passage of time and
repetition of radiotherapy fractions. It took 32days/768 hours from beginning
to complete the planned dose of 5 Gy in 10fractions delivered in twice weekly
schedule. A total of 45 readings as compared to planned 64 readings at 12
hourly intervals could be obtained owing to practical challenges in the period
of lockdown and Corona virus disease (COVID19) pandemic.
Baseline
value of hemoglobin recorded at the beginning of radiotherapy was 7.2 g/dl;
which increased to 8.8 g/dl at 816 h after start of first fraction. An increase
of 1.6 g/dl over 34 days following a linear trend as shown in (Figure 2). The values of TLC and ANC (Figure
3) however followed a different pattern. Both decreased for a short time
period followed by an increase; a pattern that repeated itself with each
fraction of EBRT delivered. More interestingly the ANC
The thrombocytopenia (Figure 4)
measured at baseline (12500/mm3) when followed over the course of
treatment decreased (following individual fraction) and increased subsequently
to again decrease following subsequent fraction followed by increase; a trend
that repeated throughout the course. Platelet count at the end of 5Gy was more
or less stayed around 15000/mm3, which had reached a nadir of <5000/mm3
twice during the course accompanied by physical signs of petechiae and
ecchymosis managed with transfusion of Random Donor Platelets [RDP].
DISCUSSION
Splenomegaly and
associated symptoms such as upper abdominal/left flank pain, early satiety,
malaise, bleeding, and features of cytopenias require intervention apart from
addressal of primary etiology. Symptoms caused are by either the mass effect or
sequestration of blood elements owing to congestive splenomegaly [2]. Spleen
radiotherapy is carried out using external beam technique with variable total
dose, dose per fraction and treatment schedules. Available literature suggests
total doses in the range of 0.15-30.5 Gy and fraction doses in the range of 0.1-2.5
Gy have been used respecting the radiation sensitivity of spleen, primary
etiology, co-morbidities and dose at which palliation is achieved [3]. The said
patient had grade-3 anemia/neutropenia and grade-4 thrombocytopenia at baseline
apart from upper abdominal pain and malaise secondary to CLD and PH other than
existing co-morbidities [4]. Though young she was planned for a total splenic
irradiation dose of 5Gy in 10 fractions delivered twice weekly owing to the
concerns for adverse events mainly hematological [5]. The EBRT technique used
was VMAT for better conformation of doses to spleen rather than surrounding
structures.
It was interesting
to observe the hemoglobin value increasing almost in a linear trend following
each fraction of EBRT to a total increase of 1.6 g/dl in 34 days. In a case
series reported by Liu et al. [6] it was reported that the hemoglobin level
didn’t raise after splenic irradiation (12Gy/8Fractions, 5 fractions per week)
in any of the patients (0/5) with Liver cirrhosis and portal hypertension6.
While Bruns et al. reported improved hemoglobin in 3 out of 5 patients with
splenomegaly (benign etiology) treated to a total dose of 3Gy in 0.5Gy per
fraction delivered 2-3 times per week [7]. In our study the trendlines of both
TLC and ANC followed the average values of two consecutive readings and it was
seen that following each radiotherapy fraction the TLC values dipped for a
brief duration ranging from 12-72 h followed by an increase; duration of which
ranged from 12-24 h. The graph of ANC closely hugged that of TLC and the
variation too graphically appeared similar (Figure 3). Liu et al. [6] reported
decline in TLC count in 3 out of 5 patients at the end of follow up (in one
case count wasn’t reported), Bruns et al. [7] suggested decrease in TLC count
in 2 out of 5 patients. Reported benefit in platelet count were noted in all 5
patients by Liu et al. whereas 3 out of 5 patients in series by Burns et al.
Our platelet count analysis suggested a decrease in count (median 3000/mm3)
following each time the fractional dose is delivered (median time 12 h from
dose) followed by a hike. The nadir value of platelet reported were 4000/mm3
which was manifested in the form of petechiae and ecchymosis but no
episodes of life-threatening hemorrhagic event was noted. Platelets were
transfused only when the counts went below 5000/mm3. The last
collected count of platelet/ANC (48 h after last fraction of EBRT) were 3500/mm3,
290/mm3 higher than baseline. The maximum decrease in different
corpuscular parameters following each fraction of radiotherapy as compared to
value at the time of delivery of dose occurred at a median time of 30.1-35.5 h.
Mean, median, standard deviation, range of blood parameters are reported in Table
1.
Available
literature in splenic irradiation suggests a partial or complete benefit for
symptoms/lab abnormalities was obtained in 85-90% of treated patients [8]. In
our study the patient was completely relieved of pain accompanied by 4cm
decrease in size of splenomegaly (as measured in maximum cranio-caudal
direction by CT image) and improvement in both anemia as well as
thrombocytopenia. Except for transient decrease in platelet counts and
resulting ecchymosis no other skin/gastrointestinal/infectious complications
occurred during the course of splenic irradiation in the said patient.
CONCLUSION
Splenic irradiation is a safe and effective method to improve splenomegaly and resultant hypersplenism as a result of benign etiology even in patient with multiple co-morbidity. The dynamics of change in different blood parameters may be represented by linearly increasing hemoglobin, waning and waxing TLC, ANC and platelets following a certain trend. Validation of these trends will need observation in higher number of patients and using different radiotherapy dose/fractionation scheme.
1. Bickenbach
KA, Gonen M, Labow DM, Strong V, Heaney ML, et al. (2013) Indications for and
efficacy of splenectomy for haematological disorders. Brit J Surg 100: 794-800.
2. Lv
Y, Lau WY, Li Y, Deng J, Han X, et al. (2016) Hypersplenism: History and
current status. Exp Ther Med 12: 2377-2382.
3. Sager
O, Dincoglan F, Uysal B, Demiral S, Gamsiz H, et al. (2017) Splenic
irradiation: A concise review of the literature. J Appl Hematol Blood Transfus
1: 101.
4. US
Department of Health and Human Services (2016) National Institutes of Health,
National Cancer Institute. Common Terminology Criteria for Adverse Events
(CTCAE) Version 5.0.
5. Carolinade
la Pinta, EvaFernández Lizarbe, ÁngelMontero Luis,José Antonio Domínguez
Rullán,SonsolesSancho García (2017) Treatment of symptomatic splenomegaly with
low doses of radiotherapy: Retrospective analysis and review of the literature.
Techn Innov Patient Support Rad Oncol 3-4: 23-29.
6. Liu
M.T., Hsieh C.Y., Chang T, Lin J, Huang C (2004) Radiotherapy for hypersplenism
from congestive splenomegaly. Ann Saudi Med 24: 198-200.
7. Bruns
F, Bremer M, Dettmer A, Janssen S (2014) Low-dose splenic irradiation in
symptomatic congestive splenomegaly: Report of five cases with literature data.
Rad Oncol 9: 86.
8. Zaorsky
NG, Williams GR, Barta SK, Esnaola NF, Kropf PL, et al. (2017) Splenic
irradiation for splenomegaly: A systematic review. Cancer Treat Rev 53: 47-52.
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