Effects Of Ethnicity On Allogenic Stem Cell Mobilization
Ahmet Kaya1, *Mehmet Ali Erkurt1, İrfan Kuku, Emin Kaya1, İlhami Berber1, Ahmet Sarıcı1, Soykan Biçim1, Emine Hidayet1, Fatma Hilal YAĞIN2
1Inonu University, Turgut Ozal Medical Center, Department of Hematology, Malatya,
2Inonu University, Faculty of Medicine, Department of Biostatistics and Medical Informatics, Malatya, Turkey
Received Date: 22/03/2022; Published Date: 28/04/2022.
*Corresponding author: Mehmet Ali Erkurt, Inonu University, Turgut Ozal Medical Center, Department of Hematology, Malatya, Turkey
Mail : erkurtali@hotmail.com
DOI: 10.55920/IJCIMR.2022.02.001065
Abstract
Purpose: In our study, we compared the stem cell levels collected after the mobilization regimen and the engraftment levels after allogeneic stem cell transplantation in Syrian patients and Turkish patients who received stem cell transplantation in our center. We aimed to reveal the differences in allogeneic stem cell transplantation between two ethnicities.
Methods: The data of Syrian patients and Turkish patients in our bone marrow transplant centre were analysed retrospectively. Ten patients with Aplastic Anemia, 2 with Thalassemia, 6 with Acute Myeloid Leukemia, 20 with Acute Lymphocytic Leukemia, 4 with Chronic Myeloid Leukemia, a total of 21 patients with Syrian origin and 21 patients with Turkish origin as the group were included in the study.
Results: A total of 42 people, 21 (50%) Turkish and 21 (50%) Syrian, with a mean age of 32.33±13,083 were included in the study. There is a statistically significant difference between Turkish and Syrian in terms of stem cell level. (p value: 0.01). When the effect size for the stem cell level is examined, this detected difference is clinically quite large. (effect size: 0.867).
Conclusion: The stem cell mobilization of level of Turks is significantly higher compared to Syrian so Mobilization of patients with syrian and platelet engraftment were more difficult. Like many factors, ethnicity can be effective in stem cell mobilization
Keywords: Ethnicity, Allogenic, Stem cells, Mobilization
Introduction
Allogeneic stem cell transplant (ASCT) is a treatment method for various malignant and non-malignant hematologic disorders. The pluripotent hematopoietic stem cells are usually obtained from the bone marrow or peripheral blood of a donor. The results of allogeneic bone marrow transplantation from the human leukocyte antigen (HLA) compatible sibling are much better. (1). Hematopoietic cell transplantation is a general term that covers a number of procedures in which the patient is treated with chemotherapy, radiation therapy, or both. Various strategies for hematopoietic cell transplantation have been developed and implemented depending on the patient's disease and disease stage, the hematopoietic cell donor and the source of the hematopoietic progenitor cells (2). ASCT is increasingly used to treat a variety of hematologic neoplasms and non-malignant bone marrow disorders (acquired and inherited) including inborn errors of metabolism (3). Many centers consider 55 years the limit for myeloablative ASCT, but allow lower-intensity ASCT in physically fit patients up to 75 years of age (4). The degree of myelosuppression and the duration of hematopoietic recovery differ according to many factors, including the regimen of preparation and the source of the graft (5). When infused hematopoietic stem cells begin to produce normal blood cells in the bone marrow, it is called engraftment. By definition, it is defined as the recipient's peripheral blood absolute neutrophil count of 1000 micro/L or greater than 500 for three consecutive days after hematopoietic cell transplantation. Depending on the donor, graft composition and type of preparation regimen, on average it is about 30 days after transplant (6). Aggressiveness of the underlying disease, disease status has a significant impact on the long-term survival of ASCT patients (7). Eligibility for ASCT differs between countries and institutions, and there are few strict rules about who is a suitable candidate and who is not. Instead, a decision must be made on whether the long-term and short-term risks of the transplant outweigh its benefits. Risk factors include the state of performance, comorbidity, age, adaptation, prevalence and condition of the disease, as well as the sensitivity of the tumor to standard therapy. It cannot be predicted that the patient will develop chronic graft-versus-host disease or other complications before hematopoietic cell transplantation. Patients should be informed of the possibilities and their impact on quality of life. All of these factors should be taken into account when determining the appropriateness of ASCT for an individual. The final decision on transplant eligibility should be made based on the risk-benefit assessment and the patient's needs and wishes (8). Following ASCT, patients are immunocompromised and therefore at high risk for infectious complications, especially when exposed to large crowds (9). Low socioeconomic status is considered to have a negative impact on the success of hematopoietic cell transplantation based on a retrospective analysis (10). Studie investigating this relationship suggest that race consists of a complex social, cultural and political structure rather than a biological concept. It has been observed that black patients are less likely to have hematopoietic cell transplantation for leukemia or lymphoma than white patients (11). In our study, stem cell levels of Syria ethnicity patients who had underwent ASCT in our center were compared with those of Turkish ethnicity patients.
MATERIALS AND METHODS
Our study was approved by the Inonu University Ethics Committee with the approval number 2021/2715. After the ethics committee approval, the patients who applied to İnönü University Turgut Özal Medical Center between the years 2018-2021 were analyzed retrospectively. Mobilization protocols, neutrophil and platelet engraftment time, collected CD34(+) stem cell level, and chemotherapy protocols before allogeneic stem cell transplantation were obtained from patient records. The collected stem cell levels of 21 Syrian and 21 Turkish patients were recorded. The donors of the allogeneic transplantation patients with stem cell levels in the study had the same ethnic structure. Neutrophil engraftment was considered the when the absolute neutrophil count was >0.5 × 109/L without G-CSF supplementation. Platelet engraftment was accepted when the platelet count was >20×109/L without platelet apheresis support.The patients were divided into two groups (Syrian and Turkish patients). Allogeneic stem cell apheresis forms of 42 patients were analyzed retrospectively whit ASCT at İnönü University Turgut Özal Medical Center bone marrow transplant unit. Ten patients with Aplastic Anemia(AA), 2 with Thalassemia, 6 with Acute Myeloid Leukemia(AML), 20 with Acute Lymphocytic Leukemia(ALL), 4 with Chronic Myeloid Leukemia(CML), a total of 21 patients with Syrian origin and 21 patients with Turkish origin as the control group were included in the study(table 1).The distribution of patients according to diagnoses and ages is available in Table 1.Each stem cell number was obtained by collecting CD34(+) stem cells with the help of the Spectra optia device after the patients received a mobilization regimen, and calculating the number of CD34(+) cells per kilogram.
RESULTS
Data analysis
Missing values in the PLT ENG (platelet engraftment) and NE ENG (neutrophıl engraftment )variables were assigned according to the mean. Normally distributed quantitative data were summarized as mean ± standard deviation and non-normally distributed quantitative data were summarized as median (minimum-maximum). Qualitative data were summarized by number (percentage). Independent samples t-test and Mann-Whitney U test were used where appropriate for statistical analysis. In this study, in addition to basic comparisons, effect sizes were calculated to evaluate the effects of each variables on Syrıan and Turkish groups. Effect size is defined as the size of the difference between groups (13). The general interpretation of the effect size in the literature; between 0.01-0.06 values, there is a small effect, between 0.06-0.14 a medium effect, and a value above 0.14 a large effect. p<0.05 was considered statistically significant. Python 3.9 Version and SPSS 26.0 programming languages were used for data analysis.
Basic Properties of Data
A total of 42 people, 21 (50%) Turkish with a mean age of 39.09 ± 15.07 and 21 (50%) Syrıans with a mean age of 28 ± 12.84, were included in the study (Table 1). Descriptive statistics and effect sizes of Turkish and Syrıan groups according to SCL (stem cell level), PLT ENG and NE ENG variables of the data set are given in Table 2. There is a statistically significant difference in terms of SCL (p: 0.01) and NE ENG (p: 0.034) variables of Turkish and Syrian patients. When the effect size is analyzed for SCL (effect size: 0.867) and NE ENG (effect size: 0.685)
This difference is clinically quite large. While the SCL values of the Turks were significantly higher than those of the Syrıans, their NE ENG values were significantly lower.
Table 1: Distribution of Patients Diagnoses
Abbreviations: Aplastic Anemia (AA), Thalassemia, Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myeloid Leukemia (CML)
SD: Standart deviation
Figure 4: Diffuse hyper pigmented and hypopigmented macules over trunk
Darier’s sign was Positive, Systemic examination was normal. Routine blood examination and serum biochemistry are within normal limits. Peripheral smear showed mild thrombocytosis No abnormality detected in abdominal sonography. H&E –Diffuse infiltration of round to spindle shaped mononuclear cells in dermis. Toluidine blue and giemsa stain showed metachromatic granules in mast cells. Immunohistochemistry – Mast cells showed strong positivity with CD117 . CD1a and CD 68 were negative.
Figure 5: H & E section showing diffuse mast cell infiltrate in dermis
Figure 6: Toluidene blue and Giemsa stained sections showing mast cells with meta chromatic granules
CD1a
Figure 7: CD117 mast cells showing strong positivity, CD1a –Negative.
Diagnosis : Diffuse Cutaneous mastocytosis
CASE3
7 month old male baby presented with hyper pigmented raised lesion and a few discrete hyper pigmented and skin colored small papules on left ankle for 4 months. History of scratching and occasional oozing of pus from the lesion present . Child is developmentally normal. On examination, Single hyperkeratotic crusted plaque 2x1 cm over left ankle and a few small hyper pigmented and skin colored papules seen. No other similar lesions over the body.
Figure 8: Hyperpigmented raised crusted plaque with a few surrounding macules over ankle joint.
CD117
Darier’s sign – Positive. Systemic examination was normal. Routine blood investigations and serum biochemistry are within normal limits. Peripheral blood smear within normal limits. Abdominal Sonography – No abnormality detected. Histopathology - Diffuse infiltration of round to oval shaped cells in superficial and deep dermis. Eosinophils seen interspersed between mononuclear cells. Metachromatic granules in Mast cells demonstrated with Toluidene blue stain Immunohistochemistry – CD117, CD1a and CD68 were negative
Figure 9: H&E stained sections showing infiltration of mast cells in dermis
Figure 10: Toluidene Blue stain , demonstration of metachromatic granules.
Figure 11 : CD117 and CD 1a Negative
Diagnosis : Mastocytoma of skin
Discussion
Mastocytosis is first described by Nettleship and Tay in 1869 and later due to the appearance like urticarial, The term Urticaria pigmentosa was coined by Sangster in 1878. Classification of Mastocytosis variants2 (WHO classification of tumors of Hematopoietic and lymphoid tissue-2017)
Cutaneous Mastocytosis
- Urticaria Pigmentosa or Maculopapular cutaneous mastocytosis.
- Diffuse cutaneous mastocytosis
- Mastocytoma of skin
Systemic mastocytosis
- Indolent systemic mastocytosis
- Smouldering systemic mastocytosis
- Systemic mastocytosis with an associated hematological neoplasm.
- Aggressive systemic mastocytosis
- Mast cell leukemia
Mast cell sarcoma
Mastocytosis can occur at any age. There is no gender difference. Cutaneous mastocytosis is most common in children and can be present at birth. About 50% of affected children develop typical skin lesions before the age of 6 months. There is a tendency of regression with age. In cutaneous mastocytosis, mast cells infiltrates remain confined to skin, whereas systemic mastocytosis is characterized by involvement of at least one extra cutaneous organ with or without evidence of skin lesion. About 10% of patients with proven systemic mastocytosis do not have skin lesions.3 The lesion of all forms may urticate when stroked (Dariers sign) and most show intra epidermal accumulation of melanin pigment. Despite variety of clinical presentation, The common picture is diffuse infiltration of mast cells in the dermis. Urticaria pigmentosa is the most common form of cutaneous mastocytosis, Lesions are larger, fewer and more papular. Diffuse cutaneous mastocytosis is less common than urticarial pigmentosa and present almost exclusively in childhood. Mastocytoma of skin, typically occurs as a single lesion, almost exclusively in children. In adult patients there is a genetic inactivation mutation of growth factor receptor C-kit and this mutation may be absent in pediatric cases and which is not associated with prognosis.4 The diagnosis is mainly clinical. Serum tryptase levels correlates with severity. Histopathological examination is essential for a definite diagnosis, The mast cells are usually oval or spindle shaped with granules that stain metachromatically with toluidine blue. They are also well demonstrated by Giemsa, tryptase or chloroacetate esterase in formalin fixed biopsies. Distinguishing between cutaneous and systemic mastocytosis in patients presenting with skin lesions depends on further investigation, including bone marrow biopsy and blood tryptase measurements.3 Prognosis depends on age, severity and clinical subtypes5 . Treatment is symptomatic with antihistamines and avoidance of drugs which may stimulate the mast cell to degranulate6 . Topical steroids also useful.
FOLLOW UP
All the 3 children showed good response to antihistamines and topical steroids, and currently doing well
CONCLUSIONS
Mastocytosis is characterized by an abnormal mast cell infiltrates. The diagnosis of cutaneous mastocytosis requires the demonstration of typical clinical findings and Histological proof of abnormal mast cell infiltration of dermis. In cutaneous mastocytosis. There is no evidence of systemic involvement in the bone marrow or any other organ. Patients with cutaneous mastocytosis without systemic involvement have a good prognosis. Careful long term follow up is essential for the early detection of systemic involvement.
Reference
- James W. Patterson. Weedon’s skin pathology. 5th ed. ELSEVIER; 2021. 155–210 p.
- Horny H P, Daniel A Arber,Steven H Swerdlow, editor. WHO classification of tumors of Hematopoietic and lymphoid tissue-2017. 4th ed. Lyon; 62–69 p.
- Arthur Rook, Darrell Wilkinson, John Ebling. Rook’s Text book of Dermatology. 9th ed. Vol. 2. WILEY Blackwell; 2016. 50.1-50.56.
- Hussain SH. Pediatric mastocytosis. Current Opinion in Pediatrics. 2020 Aug;32(4):531– 538.
- Heide R, Beishuizen A, De Groot H, Den Hollander JC, Van Doormaal JJ, De Monchy JGR, et al. Mastocytosis in children: a protocol for management. Pediatr Dermatol. 2008 Aug;25(4):493–500.
- Chatterjee S, Mukherjee S, Sinha M. Diffuse cutaneous mastocytosis in an infant. Indian J Paediatr Dermatol. 2016;17(3):209
