Case Report: Long-Term Survival of a Dog With Chronic Lymphocytic Leukemia Treated With Chlorambucil, Prednisolone, and Imatinib

A 7-year-old castrated male Poodle dog presented with chronic progressive lymphocytosis. Hematologic and peripheral blood smear findings included remarkable lymphocytosis with well-differentiated small lymphocytes. Cytology of bone marrow aspirate showed hypercellular integrity with infiltration of small mature lymphocytes, accounting for 45% of all nucleated cells. Flow cytometry of blood and marrow samples revealed neoplastic lymphocytes predominantly expressing the CD21 molecule. B-cell chronic lymphocytic leukemia (CLL) was diagnosed on an immunophenotypic analysis. Administrations of prednisolone and chlorambucil were initiated and the response was unremarkable. Therefore, additional treatment with imatinib was provided, which resolved the hematologic abnormalities associated with CLL. Flow cytometry after ~1 year of treatment showed normalization of the count of lymphocytes positive for CD21 and resolved hematologic lymphocytosis. The dog was followed-up for 2 years, and there were no severe adverse effects. This case indicates that imatinib may be a good option as an adjunctive therapy with prednisolone and chlorambucil treatment for CLL in dogs without treatment response.

Bone marrow aspirate concentrate versus platelet-rich plasma for treating knee osteoarthritis: a one-year non-randomized retrospective comparative study

Background Knee osteoarthritis (OA) is a debilitating condition affecting human body biomechanics and quality of life. Current standard care for knee OA leads to trivial improvement and entails multiple adverse effects or complications. Recently, investigational cell therapies injected intra-articularly, such as bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP), have shown safety and therapeutic potency providing patients with pain relief. In the current retrospective comparative study, we investigated the differences in pain and functional improvements in patients with symptomatic knee OA receiving intra-articular injections of BMAC vs PRP. Methods Pain and functionality scores were measured at baseline and at different time points post-injection over 12 months, using 3 self-administered, clinically validated questionnaires: the visual analogue scale (VAS) for assessing pain intensity, the knee injury and osteoarthritis outcome score (KOOS) for evaluating functionality and knee-related quality of life, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) for evaluating physical function. The repeated-measures general linear model with Sidak test for pairwise comparisons was used to investigate the influence of the treatment on the score evolution within groups (between baseline and each time point) and between groups (overall). Results The BMAC group (n = 26 knees) significantly improved in VAS, KOOS, and WOMAC scores between baseline and 12 months (57.4, 75.88, and 73.95% mean score improvement, respectively). In contrast, the PRP group (n = 13 knees) witnessed nonsignificant improvement in all scores. BMAC, in comparison to PRP, induced significant improvement in outcomes by 29.38% on the VAS scale, 53.89% on the KOOS scale, and 51.71% on the WOMAC scale (P < .002, P < .01, P < .011, respectively). Conclusions Intra-articular autologous BMAC injections are safe, effective in treating pain, and ameliorate functionality in patients with symptomatic knee OA to a greater extent than PRP injections. Graphical abstract Intra-articular autologous BMAC therapy is safe and provides more relief to patients with symptomatic knee osteoarthritis compared to PRP therapy.

HIV Myelopathy- A cross-sectional study of constellation of bone marrow findings in HIV/AIDS

Introduction and Aim: Haematological manifestations in HIV disease is common and can happen at any phase during the disease course. Anemia and thrombocytopenia are the most frequent hematologic abnormalities and are associated with high morbidity and mortality. The objective of current study was to observe and analyse various spectrum of bone marrow changes and haematological abnormalities in HIV/AIDS and to correlate findings with CD4 count. Material and Methods: A total of 44 patients over a period of 5 years were included. Clinical findings, hematological profile, bone-marrow aspirate, biopsy findings and CD4 count of these patients were documented. The association between absolute lymphocyte count (ALC) and CD4 count were further established. Results: The most common clinical indication for bone-marrow aspiration and trephine biopsy was pancytopenia (47.3%), pyrexia of unknown origin (15.1%), and unresolving hepatosplenomegaly (13.6%). Anemia (72.7%) was commonest haematological abnormality. Bone marrow aspirate was normocellular in majority of patients. Marrow findings were correlated with CD4 count and were found to be statistically significant. Tri-lineage dysplasia was observed in 9.1% of patients, and megakaryocytic dysplasia being the commonest(61.4%). Histiocytic aggregates (27.3%) were noted among which 6.8% showed acid fast bacilli in Ziehl-Neelsen stain. Fungal stains revealed histoplasmosis in 4.5% patients. Conclusion: There was a strong negative association between presence of anemia and dysplasia and CD4 count. When CD4 was <200/µL and ALC<1000/mm3, presence of anemia and dysplasia affecting various cell lines were commonly observed; therefore, can be used as indicators to assess the severity of the disease.

Intraosseous Injection of Autologous Bone Marrow Aspirate Concentrate and Platelet-Rich Plasma for Treatment of Knee Osteoarthritis

The aim of the study was to determine the effectiveness of autologous bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) intraosseous injection in the treatment of patients with knee OA stages II-III. Materials and Methods. The multicenter randomized study involved 40 patients (27 women, 13 men, average age 67.07.8 years, BMI 32.74.8, duration of disease 17.33.7 months) with knee OA of stages II-III according to the Kellgren-Lawrence (K-L) classification. Patients of the main (BMAC group) group (n = 19) underwent a single intraosseous injection of BMAC, in the comparison group (n = 21) a PRP injection (PRP group). The results were evaluated after 1, 3, 6, 12 months with the verbal rating scale (VRS), VAS, Leken and WOMAC scales. Results. Comparison of the results in the groups on the VRS showed that at an earlier time (3 and 6 months), the preferences of patients were in favor of the treatment of BMAC (65% and 55% positive reviews) before PRP (55% and 45% positive reviews), whereas after 12 months the differences were insignificant. Analysis of VAS indicators in patients of both groups indicated a more pronounced decrease in the severity of pain syndrome after BMAC intraosseous injection. The analysis of the Leken scale indicators showed in favor of BMAC throughout the entire observation period, the differences were most pronounced in the first 3 months of observation. The ratio of the values of the WOMAC index in both patients groups indicated statistically significant differences that persisted in all periods of follow-up, the increase in indicators occurred to a lesser extent after the introduction of BMAC compared with PRP. Conclusion. A single intraosseous BMAC injection has an advantage over a similar PRP injection in terms of pain, knee function and physical activity of patients at all follow-up periods. Both methods of treatment are equally safe.

High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared With Traditional Bone Marrow Aspiration Technique

Background: Bone marrow aspirate (BMA) is a common source for harvesting mesenchymal stem cells (MSCs), other progenitor cells, and associated cytokines and growth factors to be used in the biologic treatment of various orthopaedic pathologies. The aspirate is commonly centrifuged into a concentrated volume that can be immediately administered to a patient using commercially available kits. However, the handling and efficacy of BMA concentrate (BMAC) are still controversial. Purpose: To characterize BMA versus BMAC for MSC quantity, potency, and cytokine profile. Study Design: Controlled laboratory study. Methods: From 8 participants (age, 17-68 years), 30 mL of bone marrow was aspirated by a single surgeon from either the proximal humerus or distal femur and was separated into 2 equal samples. One sample was kept as BMA, and the other half was centrifuged into BMAC. The 2 samples then underwent flow cytometry for detection of MSCs, cell analysis for colony-forming units (CFUs), and cytokine profiling. A 2-tailed t test was used to detect differences between MSCs, CFUs, and cytokine density concentrations between BMA and BMAC. Results: The average concentration of MSCs in both BMA and BMAC was 0.001%. Average MSC events detected by flow cytometry were significantly higher in BMA versus BMAC (15.1 and 8.1, respectively; P < .045). Expanded MSCs demonstrated similar phenotypes, but CFUs were significantly increased in BMA compared with BMAC (104 vs 68 CFUs, respectively; P < .001). Total protein concentration and cytokine profiling demonstrated great variability between BMA and BMAC and between patients. Most importantly, BMAC failed to concentrate MSCs in 6 of 8 samples. Conclusion: There is great variability in MSC concentration, total protein concentration, and cytokine profile between BMA and BMAC. Clinical Relevance: When studying the clinical efficacy of BMAC, one must also evaluate the sample itself to determine the presence, concentration, and potency of MSCs if this is to be considered a cell-based therapy. Further standard operating procedures need to be investigated to ensure reproducible results and appropriate treatments.

Treatment of Full-Thickness Acetabular Chondral Flaps During Hip Arthroscopy: Bone Marrow Aspirate Concentrate Versus Microfracture

Background: The optimal treatment strategy for patients with full-thickness chondral flaps undergoing hip arthroscopy is controversial. Purpose: To compare functional outcomes of patients who underwent bone marrow aspirate concentrate (BMAC) application with those of patients who underwent microfracture. Study Design: Cohort study; Level of evidence, 3. Methods: This was a retrospective case series of prospectively collected data on patients who underwent arthroscopic acetabular labral repair by 1 surgeon between June 2014 and April 2020. The inclusion criteria for this study were age ≥18 years, preoperative radiographs of the pelvis, arthroscopic acetabular labral repair, exposed subchondral bone with overlying chondral flap seen at the time of hip arthroscopy, microfracture or BMAC to address this lesion, and completed patient-reported outcome measures (PROMs) (International Hip Outcome Tool–33 [iHOT-33], Hip Outcome Score–Activities of Daily Living [HOS-ADL], Hip Outcome Score–Sports Subscale [HOS-Sport], modified Harris Hip Score [mHHS], and visual analog scale [VAS] for pain) at enrollment and 12-month follow-up. Clinical outcomes were assessed using PROM scores. Results: A total of 81 hips with full-thickness chondral flaps were included in this study: 50 treated with BMAC and 31 treated with microfracture. There were no significant differences between groups in age, sex, body mass index, tear size, radiographic osteoarthritis, or radiographic femoroacetabular impingement. In the BMAC cohort, all PROM scores improved significantly from preoperatively to follow-up: 41.7 to 75.6 for iHOT-33, 67.6 to 91.0 for HOS-ADL, 41.5 to 72.3 for HOS-Sport, 59.4 to 87.2 for mHHS, and 6.2 to 2.2 for VAS pain ( P < .001 for all). In the microfracture cohort, the score improvements were 48.0 to 65.1 for iHOT-33 ( P = .001), 80.5 to 83.3 for HOS-ADL ( P = .275), 59.2 to 62.4 for HOS-Sport ( P = .568), 70.4 to 78.3 for mHHS ( P = .028), and 4.9 to 3.6 for VAS pain ( P = .036). Regarding clinically meaningful outcomes, 77.6% of the BMAC group and 50.0% of the microfracture group met the minimal clinically important difference for iHOT-33 at the 12-month follow-up ( P = .013). Conclusion: Patients with full-thickness chondral flaps at the time of hip arthroscopy experienced greater improvements in functional outcome scores at the 12-month follow-up when treated with BMAC as opposed to microfracture.