Background: Beta 2- micro globulin (β2-MG) is involved in human malignancies. Increased synthesis and release of β2-MG, as indicated by elevated serum, plasma, or urine β2-MG concentration, occurs in several malignant diseases.
Objective: The study was designed to assess the role of serum Beta2- micro globulin in the support of the diagnosis of different types of pediatric malignancies.
Subjects and Methods: This case - control study was carried out on 137 children and adolescents with newly diagnosed pre-treated malignant diseases who were admitted to pediatric oncology center at Basra Children’s Specialty Hospital, their ages ranged from 3 months to 15 years, during the period from the 1st of November 2014 till the end of October 2015, 71 were males and 66 were females and 148 healthy children and adolescents (83 were males and 65 were females) matched for age and sex regarded as control group. Cases and control characteristics were assessed from data collection by special questionnaire. All patients and control group were investigated for Beta2- microglobulin by the enzyme-linked immunosorbent assay.
Results: The study had revealed that level of Beta2-microglobulin was significantly higher in patients with malignancy in comparison to control group, P value < 0.001.Also the serum Beta2- microglobulin level for both hematological malignancies and solid malignancies was assessed and it was found that significantly higher percentage of elevated serum Beta2- microglobulin level was present in patients with hematological malignancies in comparison to solid malignancies, P value <0.01.The study also had revealed that there was a significant correlation between the initial white blood cells count ≥ 50000 cells/ml and abnormal serum Beta2- microglobulin level, P value < 0.01,but there was no significant differences in serum Beta2- microglobulin level in relation to risk groups and immunophynotypes of acute lymphoblastic leukemia ,morphological subtypes of acute myloid leukemia, stages of each type of lymphoma (Hodgkin lymphoma and non-Hodgkin lymphoma) and the histopathological subtypes of non-Hodgkin lymphomas. After subjecting variables (specific to acute lymphoblastic leukemia) to logistic regression analysis, the significant independent risk factor that associated with abnormal serum Beta2- microglobulin level was high initial white blood cells count (≥50000 cells/ml).
Conclusion: Serum Beta2- microglobulin level is significantly higher in patients with hematological malignancies and high initial white blood cells count(≥50000cells/ml) .From this study, serum Beta2- microglobulin could be recommended in the initial work up for diagnosis of childhood malignancy.
Rimmel Yosra Kanoun*, Nour Ben Abdeljelil, Sabrine Mekni, Manel Kasdallah, Rihab Ouerghi, Insaf Ben Yaiche, Lamia Torjemane, Dorra Belloumi, Ines Turki, Ines Safra, Saloua Ladeb and Tarek Ben Othman
Published on: 14th April, 2023
Background: Measurable residual disease (MRD) status before allogeneic hematopoietic stem cell transplantation (AHSCT) is commonly associated with a high risk of relapse. It is still uncertain whether AHSCT could overcome the negative impact of MRD positivity (MRD+), especially in patients with high-risk Philadelphia negative acute lymphoblastic leukemia (Ph-negative ALL).
Materials and methods: An observational retrospective study was conducted on patients with high-risk Ph-negative ALL who underwent AHSCT between January 2005 and June 2022. The patients selected were in complete remission (CR): with 80% in CR1 (n = 69) and 20% in CR2 (n = 17). Graft sources were bone marrow (BM) in 71% of patients and peripheral blood stem cells in 29% of patients. The conditioning regimen was TBI or chemotherapy-based (CT). Bone marrow MRD level was quantified using 4-6 color multiparametric flow cytometry (MFC). The threshold for MRD positivity was ≥ 0.1%.
Results: The study included 86 patients (45 B-ALL and 41 T-ALL) with a median age of 18 years (range, 4–55 years). The median level of MRD pre-AHSCT (pre-MRD) was 0.4×10-3 (range, 0.01-75.6×10-3). After a median follow-up of 25 months (range 1-205 months), the cumulative incidence of relapse (CIR) was significantly higher in the MRD+ group (39% vs. 20%, p = 0.04). The median time of relapse post-AHSCT was 14 months (range, 1-203 months) in the MRD+ group and 32 months (range, 4-209 months) in the MRD- group (p = 0.28). Non-relapse mortality (NRM) was 15% in both groups (p = 0.97). The 2-year estimated overall survival (OS) and event-free survival (EFS) were 61% vs. 74% (p = 0.07) and 58% vs. 70% (p = 0.10) in the MRD+ and MRD- groups, respectively. A subgroup analysis in MRD+ patients showed that a TBI-based conditioning regimen was distinctly associated with lower CIR (22% vs. 60% respectively, p = 0.04), improved OS (82% vs. 36% respectively, p = 0.007) and better EFS (73% vs. 38%, p = 0.04) compared to CT-based. In a multivariate analysis, pre-AHSCT MRD+ status and non-TBI-based conditioning were significantly associated with inferior OS (OR, 2.30; 95% CI, [1.027-5.168], p = 0.04 and OR, 3.91; 95% CI, [1.624-9.418], p = 0.002, respectively). The only predicting factor of lower EFS was the non-TBI-based regimen (OR, 2.82; 95% CI, [1.308-6.097], p = 0.008). Non-TBI-based and CR2 were significantly associated with higher CIR (OR, 6.25; 95% CI, [1.947-20.055], p = 0.002 and OR, 4.74; 95% CI, [1.197-18.791], p = 0.03, respectively). Peripheral stem cell source was significantly associated with higher NRM (OR, 6.55; 95% CI, [1.488-28.820], p = 0.01).
Conclusion: High-risk Ph-negative ALL patients with MRD ≥ 10-3 prior AHSCT had lower OS compared to MRD- patients and may benefit from TBI as a conditioning regimen before AHSCT.
Khalid Ahmed Al-Anazi*, Alsaffar WA, Aljishi FK, Kanfer S, Kalogiannidis P, Alenazi W, Alshammasi Z, Albahrani A, Abduljalil O, Mutahar E, Alwakeel AM, Apostolidis I, Darweesh M, Almokhtar N, Abdulbaqi M, Albanyan O, Alshaibani Z, Raslan H and Aldayel A
Published on: 15th March, 2024
Background: Patients with acute and chronic leukemia presenting with hyperleukocytosis are at risk of developing leukostasis which has serious and life-threatening complications. Leukapheresis is usually performed to reduce the complications of leukostasis in patients presenting with hyperleukocytosis and clinical manifestations compatible with leukostasis. Methods and materials: A retrospective study of patients with acute and chronic leukemia who received leukapheresis for hyperleukocytosis between the 1st of January 2013 and the 31st of December 2023 at King Fahad Specialist Hospital (KFSH) in Dammam, Saudi Arabia was performed. Results: Over a period of 11 years, a total of 50 patients with acute and chronic leukemia presenting with hyperleukocytosis and clinical manifestations of leukostasis; 32 patients with acute leukemia (AL) and 18 patients with chronic myeloid leukemia (CML); received leukapheresis at our institution. Among the 32 patients with AL who received leukapheresis, 24 patients (75%) had acute myeloid leukemia (AML), 7 patients (21.88%) had acute lymphoblastic leukemia (ALL) and 1 patient (3.13%) had bilineage acute leukemia (BAL). At presentation of their AL: 3 patients (9.38%) had fever, 9 patients (28.13%) had infections, 4 patients (12.5%) had palpable spleen or liver, 6 patients (18.75%) had palpable external lymph nodes, and 9 patients (28.13%) had extramedullary disease (EMD). After receiving induction and consolidation cycles of chemotherapy, 11 patients (34.38%) of AL patients received allogeneic hematopoietic stem cell transplantation (HSCT). At the end of the follow-up, 17 patients (53.1%) with AL were alive while 15 patients (46.9%) were dead. The 8-year overall survival (OS) for all patients with AL subjected to leukapheresis was 47%. The 5 years OS for patients with AL who subsequently received HSCT and those who did not receive allogeneic HSCT were 70% and 40% respectively. The mean white blood cell (WBC) count of CML patients subjected to leukapheresis was 465.5 × 109/L, 11 patients (61.11%) had clear signs of leukostasis, and 8 patients (44.44%) had splenomegaly at presentation. Regarding the disease stage at presentation, 14 CML patients (77.78%) had chronic phase (CP), 2 patients (11.11%) had accelerated phase (AP) and 2 patients (11.11%) had blast phase (BP). Regarding the fate of CML patients at the end of the study were: 15 (83.33%) were alive, 1 (5.56%) dead, and 2 (11.11%) were unknown as they lost follow-up. However, the 10-year OS of patients with CML subjected to leukapheresis was 90%. Conclusion: Patients with acute or chronic leukemia presenting with hyperleukocytosis and either ongoing or impending leukostasis should have urgent cytoreductive chemotherapy and leukapheresis to prevent life-threatening complications. Although the outcome of AL patients presenting with leukostasis is generally poor, prompt cytoreductive therapy and leukapheresis, followed by induction chemotherapy and allogeneic HSCT may improve the outcome. Also, urgent cytoreduction including leukapheresis improves the outcome of patients with CML presenting with hyperleukocytosis and leukostasis.
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