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Journal of Stem Cell Therapy and Transplantation
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This is an Open Access Journal

Open Access journal
ISSN (Online) 2577-1469
Published by Heighten Science Publication Corporation

[23 journals]

Role of measurable residual disease quantified by 4 to 6 color flow
cytometry before allogeneic hematopoietic stem cell transplantation for
high-risk Philadelphia-negative acute lymphoblastic leukemia
- Authors: 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, Tarek Ben Othman
  Abstract: 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.
  PubDate: 2023-04-14 09:54:48
Outcome of Outpatient Autologous Hematopoietic Stem Cell Transplantation
in Patients with Multiple Myeloma and Relapsed and Refractory Hodgkin
Lymphoma. The Experience of King Fahad Specialist Hospital in Dammam,
Saudi Arabia
- Authors: Khalid Ahmed Al-Anazi; Alshami A, Mutahar E, Abduljalil O, Kanfer S, Kaloyannidis P, Bacal J, Estanislao A, Apostolidis I, Almokhtar N, Darweesh M, Abdulbaqi M, Alenazi W, Alshammasi Z, Albanyan O, Ayyad A, Alsomali Z, Albatran M, Raslan H, Albahrani A, Alsaber A, AlMulhem N, Dridi W, Alrabeh R, Abu Rahma F, Nightingale F, Ahadai P, Alhashmi H
  Abstract: Background: Autologous hematopoietic stem cell transplants (HSCT) is the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (MM) and patients with relapsed and refractory Hodgkin lymphoma (R/R-HL) who achieve chemosensitivity after salvage therapy. Although autologous HSCT is routinely performed in an inpatient setting, the procedure can safely be performed in an outpatient setting.Methods and materials: A retrospective study of patients with MM and R/R- HL who received outpatient autologous HSCT at King Fahad Specialist Hospital (KFSH) in Dammam, Saudi Arabia between the first of April 2017 and the 31st of January 2022 was performed.Results: Over the study period of 4 years and 10 months, a total of 90 outpatient autologous HSCTs were performed for 79 patients (54 patients with MM; 4 of them received planned tandem autografts and 7 other myeloma patients received second autologous HSCTs for relapsed or progressive disease; and 25 patients with R/R-HL) at our institution. The median ages of patients with MM and those with R/R-HL at HSCT were 50.4 years and 27.8 years respectively.At the presentation of their MM, the following high-risk (HR) features were encountered: stage II and III diseases according to the revised international scoring system (RISS) in 53.7%; adverse cytogenetics in 42.6% and extensive bone involvement in 53.7% of patients. In patients with HL at presentation, 48% of patients had stage IV disease according to Ann Arbor staging classification and 84% of patients had B symptoms.Survival for 100 days post-HSCT for all patients with MM and HL who received outpatient autologous transplants was 100%. For patients with MM, the overall survival (OS) rates at 3 years and 4 years post-HSCT were 80% and 67%, while the progression-free survival (PFS) rates over 3 years and 4 years were 58% and 38% respectively. For patients with HL, the OS at 6 years post-HSCT was 95% while the PFS rates at 3 years and 6 years post-HSCT were 84% and 62% respectively.Conclusion: Outpatient autologous HSCT for patients with MM and HL is safe, and feasible and can lead to short-term as well as long-term outcomes that are comparable to autologous transplantation performed in an inpatient setting. Additional benefits of outpatient autologous include saving beds and reducing hospital costs.
  PubDate: 2023-03-08 15:01:54
The complement cascade as a target against SARS-CoV-2-induced
pneumonia
- Authors: Gianluigi Ferretti
  Abstract: Fox, et al. [1] reported on the relevant cardiopulmonary findings in a series of autopsies of patients deceased from SARS-CoV-2 infection. In particular, regarding the histologic examination of the lungs, they observed bilateral diffuse alveolar damage with a lymphocytic infiltrate, thickened alveolar capillaries, fibrin thrombi within the capillaries and small vessels, and entrapment of neutrophils, without any significant neutrophilic, infiltrate within airways or the interstitium.
  PubDate: 2023-02-14 17:07:12
Validation of Kinetic Stem Cell (KSC) counting algorithms for rapid
quantification of human hematopoietic stem cells
- Authors: James L Sherley; Michael P Daley, Renly A Dutton
  Abstract: Specific quantification of therapeutic tissue stem cells (TSCs) is a major challenge. We recently described a computational simulation method for accurate and specific counting of TSCs. The method quantifies TSCs based on their unique asymmetric cell kinetics, which is rate-limiting for TSCs’ production of transiently-amplifying lineage-committed cells and terminally arrested cells during serial cell culture. Because of this basis, the new method is called kinetic stem cell (KSC) counting. Here, we report further validations of the specificity and clinical utility of KSC counting. First, we demonstrate its quantification of the expected increase in the hematopoietic stem cell (HSC) fraction of CD34+-selected preparations of human-mobilized peripheral blood cells, an approved treatment product routinely used for HSC transplantation therapies. Previously, we also used the KSC counting technology to define new mathematical algorithms with the potential for rapid determination of TSC-specific fractions without the need for serial culture. A second important HSC transplantation treatment, CD34+-selected umbilical cord blood (UCB) cells, was used to investigate this prediction. We show that, with an input of only simple population doubling time (PDT) data, the KSC counting-derived “Rabbit algorithms” can be used to rapidly determine the specific HSC fraction of CD34+-selected UCB cell preparations with a high degree of statistical confidence. The algorithms define the stem cell fraction half-life (SCFHL), a new parameter that projects stem cell numbers during expansion culture. These findings further validate KSC counting’s potential to meet the long-standing unmet need for a method to determine stem cell-specific dosage in stem cell medicine.
  PubDate: 2022-11-28 17:42:04
The outcome of autologous hematopoietic stem cell transplantation in
patients with multiple myeloma. The experience of King Fahad Specialist
Hospital in Dammam, Saudi Arabia
- Authors: Khalid Ahmed Al-Anazi; Mutahar E, Abduljalil O, Kanfer S, Kaloyannidis P, Estanislao A, Apostolidis I, Almokhtar N, Darweesh M, Abdulbaqi M, Alenazi W, Alshammasi Z, Alshaibani Z, Kawarie M, Raslan H, Albahrani A, Alsaber A, AlMulhem N, Dridi W, Aldayel A, Alrabeh R, Alshami A, Ayyad A, Abu Rahma F, Lardizabal J, Salam A, Haque K, Alsagheir A, Alhashmi H
  Abstract: Background: Aautologous hematopoietic stem cell transplants (HSCT) is the standard of care for newly diagnosed patients with multiple myeloma (MM) who are eligible for autologous transplantation. Although cryopreservation is routinely employed, autologous HSCT can be performed using non-cryopreserved stem cells.Methods and materials: A retrospective study of patients with MM who received autologous HSCT between the 10th of October 2010 and the 31st of January 2022 at King Fahad Specialist Hospital (KFSH) in Dammam, Saudi Arabia was performed.Results: Over 11 years and 113 days, a total of 135 autologous HSCTs were performed for 119 patients with MM at our institution. Single autologous HSCTs were performed for 119 patients, while 16 of these patients received either planned tandem autologous transplants or second autografts due to either progression or relapse of their myeloma. The median age of patients with MM at autologous HSCT was 51.5 years. At presentation of their MM, the following high-risk (HR) features were encountered: stage III disease according to the revised international scoring system (RISS) in 12.3%; adverse cytogenetics in 31.93% of patients; advanced bone disease in 60.50%; and renal dysfunction or failure in 11.76% of patients. A total of 104 autologous HSCTs (77.04%) were performed without cryopreservation while 31 autografts (22.96%) were performed using cryopreserved apheresis stem cell products. Additionally, 54 autologous HSCTs (40.00%) were done at outpatient while 81 autografts (60.00%) were performed in an inpatient setting. Survival for 100 days post-HSCT for all patients with MM who received autologous transplants including those done at outpatient was 100%. The 4 years overall survival (OS) an progression-free survival (PFS) for patients with MM who received non- cryopreserved or fresh autologous HSCTs were 82% and 68% respectively.Conclusion: Autologous HSCT without cryopreservation is safe, and feasible and can lead to short-term as well as long-term outcomes that are comparable to autologous transplantation with cryopreservation. Non- cryopreserved autologous grafts allow the performance of autologous transplants in an outpatient setting to save beds and reduce costs.
  PubDate: 2022-09-29 17:46:13
Use of collagenase to isolate adipose tissue-derived stem cells –
substantial manipulation or not'
- Authors: Koellensperger Eva; Gramley Felix, Germann Guenter, Leimer Uwe
  Abstract: Background: Collagenase is commonly used to isolate the stromal vascular fraction (SVF) or adipose tissue-derived stem cells (ADSCs) from human adipose tissue. Enzymatic breakdowns may be a substantial manipulation according to the classifications of medical regulatory authorities. This study investigates the possible effects of human adipose tissue dissociation with collagenase on in vitro function and behavior of ADSCs.Methods and results: Adipose tissue from nine donors was divided into two equal fractions. SVF was then isolated either mechanically or with collagenase, respectively. The resulting cells were analyzed for their surface markers directly after isolation and at passage five. Proliferation, tri-lineage differentiation, and secretome markers were measured after passage four.Using collagenase compared to mechanical isolation did not alter the expression of typical surface markers of ADSCs. ADSCs isolated with collagenase showed a significantly shorter population doubling time (p < 0.001), a significantly higher mean specific GPDH-activity, a stronger intensity in perilipin staining (p = 0.005), and a significantly higher extracellular calcium deposition (p = 0.006) than mechanically isolated ADSCs. The expression of adipogenic and osteogenic marker genes was not different in mechanically versus enzymatically isolated ADSCs. There were no significant differences in proteoglcyan production (p > 0.05) and the concentration of type 2 collagen. Except for an increased CCL2 concentration in mechanically isolated ASDCs (p = 0.01), there were no significant differences in the concentration of secreted proteins between both isolation methods. Conclusions: The use of collagenase does not substantially impair central in vitro characteristics and functions of human adipose tissue-derived stem cells.
  PubDate: 2022-08-30 10:30:14
Allogeneic hematopoietic cell transplantation to treat two synchronous
hematologic malignancies
- Authors: Enrico Santinelli; Raffaella Cerretti, Gottardo De Angelis, Benedetta Mariotti, Giulia Ciangola, Camilla Page, Elisa Lindfors Rossi, Gianmario Pasqualone, William Arcese
  Abstract: Allogeneic hematopoietic cell transplantation often represents the only solution for several poor-prognosis hematologic malignancies. The curative strategy for patients with synchronous hematologic disorders is always difficult and, in most cases, ineffective. Herein, we report an unusual case of synchronous hematologic disorders successfully treated with an “ad-hoc” conditioning regimen followed by allogeneic hematopoietic cell transplantation.
  PubDate: 2022-06-10 09:42:36
Age-related changes in cell yield and viability of feline Adipose
Tissue-Derived Mesenchymal Stem (fAD-MSCs)
- Authors: Shazia Nissar; Geetha Ramesh, Sabiha Hayath Basha, TA Kannan, Shahid Hussain
  Abstract: In the present study, omental adipose tissue was collected from, the animals that underwent ovariectomy and ovariohysterectomy, surgical procedures, at the age of seven months to 11/2 years of age groups. The sample was digested with 0.1% (W/V) collagenase type I and transferred to a beaker with a magnetic stirrer and kept in a stirrer with 600 rpm at 37 °C for 30 minutes. The viability of the cell was evaluated by the trypan blue exclusion method using a hemocytometer. Trypan blue had a high affinity to nuclear DNA, which traverse the member in a dead cell and dye it blue. In the present study, the cell yield of fAD-MSCs was 8.15 ± 0.68, 6.55 ± 0.26, 4.85 ± 0.42, 3.90 ± 0.34, and 3.51 ± 0.43 in different age groups viz., 7,8,9 month 1 and 1½ year respectively. In younger age groups, cell yield and viability percentage were more than in animals of higher age groups. In the younger age group, stem cells proliferation status is considered potent for therapeutic application.
  PubDate: 2022-04-01 17:37:58