Background
AIDS, the most common cause of morbidity and mortality globally, causes more than 1.1 million deaths annually of individuals mostly older than 15 years old. With the introduction of antiretroviral therapy, serious non-AIDS complications (for example malignancies) have occurred, which have a mortality risk twice that of AIDS-related events [
1,
2]. AIDS-Related Lymphoma (ARL) is a common malignancy in the HIV-infected population [
3]. The risk of developing lymphoma steadily increases with an increasing duration of HIV infection and advancing immunosuppression [
4,
5].
Patients who develop ARL are generally reactive to chemotherapy, with some reportedly cured by chemotherapy [
6]. However, the chemotherapy was myelotoxic, and 75 and 52% of patients experienced grade 4 neutropenia and thrombocytopenia respectively. The treatment-related mortality rate is 10% [
7]. Additionally, chemotherapeutic drugs can cause organ damage and bone marrow suppression, and potentially causing even more severe immune damage to people with AIDS [
8]. Therefore, bone marrow suppression should be addressed for patients being treated with chemotherapy, especially patients whose immune system is compromised as a result of their disease. It is essential to refine the investigational approaches to ARL treatment because the majority of patients present with advanced AIDS and poor prognostic factors, while less than one third have no adverse prognostic factors and reasonable prospects for long-term survival.
Previously, we have investigated the same treatment regimen on patients with AIDS and decompensated liver cirrhosis [
9]. We conducted infusion-port intubation through the right omental vein after splenectomy. The patient’s autologous bone marrow was collected and then transfused into the portal vein through the infusion-port. The findings confirmed that autologous bone marrow transfusion can promote liver function reconstruction without any side effects.
To investigate the effect of autologous bone marrow transfusion on the reconstruction of both bone marrow and the immune system in patients with ARL, we undertook a clinical study investigating 32 patients with ARL between March 2019 and March 2020. These patients were considered in three groups: a control group, the ABM-MVI group and the ABM-PI group. Following treatment, peripheral blood and lymphocyte diagnostic subsets were detected and documented in all patients. Before chemotherapy, each patients’ autologous bone marrow was collected and stored at − 20 °C in a preservation solution. Five days after chemotherapy, those patients with bone marrow preservation were administered the ABM via either an infusion-port or a peripheral vein. In comparison with patients that received conventional chemotherapy, the levels of white blood cells (WBC), platelets (PLT), and haemoglobin (HB) in patients treated with an autologous bone marrow transfusion after chemotherapy were significantly increased (P < 0.05). These findings, following an autologous bone marrow transfusion, indicate that the stem cells in bone marrow significantly promotes the reconstruction of bone marrow. Additionally, our data support the finding that autologous bone marrow transfusion after chemotherapy does promote the reconstruction of both the bone marrow and immune systems. There was no significant difference in the bone marrow recovery and reconstruction outcomes between those patients in the mesenteric vein transfusion group and peripheral vein transfusion group.
Our research demonstrates that autologous bone marrow transfusion can promote the reconstruction of bone marrow and the immune system following chemotherapy. These results provide insight so that better protocols and strategies can be developed for the treatment of AIDS-related diseases.
Methods
Patients
The study participants were a total of 32 ARL patients hospitalised in our centre between March 2019 and March 2002. The study group was comprised of 19 males and 13 females, aged between 22 and 70 years old. All the patients had been treated with tumour resection or biopsy. All the patients’ pathological results showed that the lesions were non-Hodgkin’s lymphoma. Detection of HIV antibodies was undertaken before surgery, and the HIV infection was confirmed at the local CDC. All patients have been treated with antiretroviral drugs.
From this patient cohort, 16 participants were treated with conventional surgery and chemotherapy (control group), while another 16 patients were treated with chemotherapy followed by autologous bone marrow transfusion via either a mesenteric vein (ABM-MVI group) or a peripheral vein (ABM-PI group). Measurements of the peripheral blood and lymphocyte diagnostic subsets were undertaken before and after chemotherapy.
Treatment
All patients were treated with antiretroviral therapy before surgery. Any additional health issues and/or diseases detected with the 32 participants were also treated before the study commenced, such as anti-tuberculosis, antifungal, and other supportive treatments. The total number of white blood cells (WBC) of patients was often lower than 2 × 109 / L, so granulocyte stimulating factors or blood transfusions were administered to patients with severe anaemia. Patients with neck cancer, axillary cancer or inguinal cancer had either the surgical resection or a biopsy of the tumours, and excised specimens were analysed by pathologists. Open surgery was conducted to remove tumours in patients with abdominal cancer, and they were monitored for postoperative complications such as intestinal obstruction and gastrointestinal bleeding. An infusion-port intubation through the right omental vein was undertaken for 8 patients. The doses and schedules of chemotherapy regimens were determined for each patient according to the pathological staging of the detected tumours.
CHOP-based Chemotherapy was administered to all 32 patients [
18]: CTX (Cyclophosphamide) 750 mg/m
2 IV day 1, ADM (Adriamycin) 500 mg/m
2 IV day 1, VCR (Vincristine, Oncovin) 1.4 mg/m
2 IV day 1, Pred (Prednisone) 100 mg PO day 1 to day 5, or add Rituximab (R-CHOP) 375 mg/m
2 IV day 1. Repeat every 3 weeks for 6 cycles.
Bone marrow collection and transfusion
Approximately 3 weeks after surgery, the bone marrow of each patient was collected before the commencement of chemotherapy treatment. Patients, lying in a supine position and under local anaesthesia, were punctured with a bone marrow biopsy needle under sterile conditions at the right or left anterior superior iliac crest. Bone marrow was collected via a special porous bone marrow collector for 50 ml. The bone marrow samples were then injected into a 100 ml plastic bag containing 50 ml of bone marrow preservation solution and stored at − 20 °C. Following 5 days of chemotherapy, the stored bone marrow was placed in a water bath at 39 °C and kept swinging for 3 min to rewarm. The bone marrow was then infused into the patient’s portal vein via the infusion-port. The abdomen was sterilized before infusion and the infusion-port rinsed and closed with normal saline. Alternatively, the bone marrow was transfused via the patients’ peripheral vein.
Statistical analyses
SPSS 16.0 statistical software was used for analysis. Measurement data were expressed as mean ± standard deviation (\( \overline{x} \) ±s), and P < 0.05 was considered statistically significant. The One-way ANOVA was used to describe the p-value in tables.
Peripheral blood and lymphocyte subsets were determined before chemotherapy. After 5 days of chemotherapy, an autologous bone marrow transfusion was undertaken. After 10 days of chemotherapy (it was also the 5 days of autologous bone marrow transfusion), routine blood and lymphocyte data subsets were re-examined and recorded for control analysis.
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