CD34+ Stem Cell Infusion for Post-Bone Marrow Transplant Care

Overseen By Elizabeth Shpall, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 4-6 weeks

200 Participants Needed

Trial Summary

What is the purpose of this trial?

Objectives: Primary Objective To provide compassionate access to the Miltenyi device for CD34+ cell infusions to patients who experience poor graft function after stem cell transplantation (SCT).

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the CD34+ Stem Cell Infusion treatment for post-bone marrow transplant care?

Research shows that CD34+ stem cells can help in rapid and stable recovery of blood cells after a bone marrow transplant, as they are crucial for producing new blood cells. In some cases, using CD34+ cells has led to successful recovery in patients with poor graft function after a transplant. ^{1 2 3 4 5}

Is CD34+ Stem Cell Infusion safe for humans?

CD34+ Stem Cell Infusion has been generally safe in humans, with no severe adverse reactions reported in studies involving patients with various conditions. Some studies noted mild to moderate adverse reactions during infusion, but these were not severe, and the procedure was well-tolerated overall. ^{6 7 8 9 10}

How is CD34+ Stem Cell Infusion different from other treatments for post-bone marrow transplant care?

CD34+ Stem Cell Infusion is unique because it involves the use of positively selected CD34+ cells, which are stem cells that can help restore the blood and immune system after a bone marrow transplant. This treatment can reduce the risk of complications like graft-versus-host disease and allows for rapid recovery of blood cells, making it a promising option compared to traditional methods. ^{2 5 11 12 13}

Research Team

Elizabeth Shpall, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients who have had a stem cell transplant but are experiencing poor or no graft function afterwards. It's not specified who can't join, so it seems open to anyone meeting the inclusion criteria.

Inclusion Criteria

My stem cell transplant did not work well or at all.

Exclusion Criteria

N/A

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an infusion of CD34 positive stem cells to improve graft function

4-6 weeks

1 visit (in-person) for infusion, weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including signs of graft versus host disease (GVHD)

4 weeks

Weekly visits (in-person) for blood tests and GVHD monitoring

Optional Additional Infusion

Participants may receive an additional infusion if the first is not effective

4-6 weeks after the first infusion

Treatment Details

Interventions

• CD34 Positive Stem Cell Infusion
• Miltenyi device

Trial Overview The trial provides access to a special device called the Miltenyi device, which is used for infusing CD34+ cells (a type of stem cell) into patients with poor graft function after bone marrow transplant.

Participant Groups

Group I: CD34 Positive Stem Cell Infusion Experimental Treatment 2 Interventions

Participants infused by vein with around 1 - 4 million/kg CD34+ selected cells. If the first infusion is not effective, an additional infusion may be given 4 - 6 weeks after the first infusion.

CD34 Positive Stem Cell Infusion is already approved in India, Japan, United States for the following indications:

Approved in India as CD34+ Cell Infusion for:

• Liver Cirrhosis
• Decompensated Cirrhosis

Approved in Japan as CD34+ Cell Therapy for:

• Critical Limb Ischemia
• Coronary Microvascular Dysfunction
• Diabetic Kidney Disease

Approved in United States as Autologous CD34+ Cell Infusion for:

• Refractory Angina
• Dilated Cardiomyopathy

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

CD34 is a specific marker for hematopoietic stem cells, and using monoclonal antibodies to select CD34+ cells could improve the efficacy of autologous bone marrow transplantation by ensuring the graft contains the necessary stem cells for recovery.

Preliminary studies indicate that isolating CD34+ cells from bone marrow is feasible and may lead to successful short-term hematopoietic engraftment in patients, suggesting a promising approach for enhancing bone marrow transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive stem cell selection--basic science. Civin, CI., Strauss, LC., Fackler, MJ., et al.[2007]

The study demonstrated that ex-vivo expansion of CD34+ blood progenitors using specific cytokines can achieve significant increases in committed precursors, with an 8-fold increase in nucleated cells and a 59-fold increase in GM-CSF responsive precursors, indicating a robust method for enhancing hematopoietic recovery after chemotherapy.

Importantly, the expansion process did not negatively impact the most immature progenitor cells, suggesting that this cytokine-mediated amplification could be beneficial for autologous transplantation without compromising the stem cell reservoir.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expansion of blood CD34 positive cells: committed precursors expansion does not affect immature hematopoietic progenitors. David, S., Rice, A., Vianes, I., et al.[2017]

Immunoselected allogeneic CD34+ blood cells were evaluated in two patients with poor graft function after bone marrow transplantation (BMT), showing that the infusion led to trilineage repopulation of bone marrow and improved blood parameters, indicating potential efficacy in treating graft failure.

While one patient unfortunately died from complications, the other patient remained stable and in remission 260 days post-infusion, suggesting that CD34+ cell therapy may be a viable option for addressing post-BMT graft failure without exacerbating graft-versus-host disease (GVHD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of poor marrow graft function with allogeneic CD34+ cells immunoselected from G-CSF-mobilized peripheral blood progenitor cells of the marrow donor. Arseniev, L., Tischler, HJ., Battmer, K., et al.[2007]

In a study of 100 healthy donors undergoing a second stem cell donation, it was found that the yields of CD34+ cells were lower compared to their first donation, indicating a decrease in effectiveness for second collections.

Factors such as steady-state lymphocyte counts and the time interval between donations influenced the number of CD34+ cells collected, with male donors and longer intervals (over 9 months) being more favorable for higher yields.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors affecting the CD34+ cell yields from the second donations of healthy donors: The steady-state lymphocyte count is a good predictive factor. Guo, ZP., Wang, T., Xu, LP., et al.[2017]

CD34(+) peripheral blood progenitor cells (PBPC) selection significantly reduces contaminating tumor cells and T cells, which can help improve outcomes in patients undergoing autologous or allogeneic transplantation.

Transplantation of positively selected CD34(+) PBPC leads to rapid and stable engraftment of neutrophils and platelets, although careful monitoring for infections is necessary, and further trials are needed to assess long-term survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of CD34(+) peripheral blood progenitor cells (PBPC). Vogel, W., Scheding, S., Kanz, L., et al.[2005]

In a study of 213 pediatric patients undergoing hematopoietic stem cell transplantation, serious adverse reactions (ARs) during cellular therapy product infusions occurred in 25% and 11% of cases, with no severe grade 4 or 5 reactions reported.

The source of stem cells significantly influenced the risk of serious ARs, with cord blood being associated with a higher risk, while manipulated cellular therapy products were found to be protective, suggesting they can help reduce adverse reactions during infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions during stem cell infusion in children treated with autologous and allogeneic stem cell transplantation. Truong, TH., Moorjani, R., Dewey, D., et al.[2018]

In a study of 215 patients receiving autologous peripheral blood progenitor cell (PBPC) infusions, 56.9% experienced infusion-related adverse reactions, highlighting the need for careful monitoring during treatment.

Factors such as female gender, multiple myeloma diagnosis, and the number of granulocytes infused per kg body weight were significant predictors of these adverse reactions, indicating that patient characteristics and graft composition play crucial roles in infusion safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity related to autologous peripheral blood haematopoietic progenitor cell infusion is associated with number of granulocytes in graft, gender and diagnosis of multiple myeloma. Bojanic, I., Cepulic, BG., Mazic, S., et al.[2011]

The infusion of CD34+ cells selected using a magnetically activated cell sorting device was found to be safe, with no adverse events reported in 54 breast cancer patients, and resulted in rapid hematological recovery, with median platelet and neutrophil recovery times of 11 and 9 days, respectively.

The CD34+ cell selection process achieved a high median purity of 96.1% and a median recovery rate of 52.3%, indicating effective performance of the selection device in preparing the cell product for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly purified CD34+ cells isolated using magnetically activated cell selection provide rapid engraftment following high-dose chemotherapy in breast cancer patients. Richel, DJ., Johnsen, HE., Canon, J., et al.[2006]

In a study of 53 procedures involving 47 patients with hematologic malignancies and solid tumors, higher initial percentages of CD34+ cells in the starting population led to better purity and enrichment of these progenitor cells in the final product, while also reducing unwanted CD3+ and CD19+ cells.

The reinfusion of selected CD34+ cells was found to be safe and well-tolerated, with no adverse reactions reported, indicating that autologous transplantation using this method is a viable option for patients undergoing myeloablative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive selection of CD34+ cells by immunoadsorption: factors affecting the final yield and hematopoietic recovery in patients with hematological malignancies and solid tumors. Bruno, A., Caravita, T., Adorno, G., et al.[2019]

The review of 18 studies on hematopoietic stem cell transplantation found that mild and moderate adverse reactions were most common, with nausea and vomiting being the most frequently reported issues.

The cardiovascular, respiratory, and gastrointestinal systems were the most affected by these adverse reactions, highlighting the need for monitoring these organ systems during and after the infusion of stem cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions on day zero of hematopoietic stem cell transplantation: integrative review. Figueiredo, TWB., Mercês, NNAD., Nunes, MBM., et al.[2022]

The study highlights the successful use of various cell sources for hematopoietic system restoration, including bone marrow, peripheral blood stem cells (PBSC), and cord blood (CB), with at least 42 allogeneic transplantations performed using CB.

Flow cytometry and clonogenic assays reveal significant differences in the characteristics of CD34+ cells from these sources, indicating that CB CD34+ cells are particularly promising due to their high proliferative potential and early myeloid progenitor status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phenotypic differences between CD34 positive cells in various transplantation tissues]. Fritsch, G., Stimpfl, M., Leitner, A., et al.[2006]

In a study of 16 patients undergoing autologous peripheral blood stem cell transplantation (auto-PBSCT) and 24 donors for allogeneic PBSCT (allo-PBSCT), it was found that auto-PBSCT patients had a significantly higher ratio of CD34+ cells in their mobilized peripheral blood compared to allo-PBSCT donors, which may impact post-transplant recovery.

The recovery of neutrophils and platelets post-transplantation was similar between both groups, indicating that the total number of infused mononuclear cells (MNCs) and CD34+ cells is crucial for effective hematopoietic reconstitution, regardless of the type of transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hematopoietic reconstitution in early period after autologous and allogeneic peripheral blood stem cell transplantation]. Wei, YQ., Feng, R., Yi, ZS., et al.[2017]

CD34+ is a key surface marker for identifying hematopoietic stem and progenitor cells, playing a role in cell adhesion and possibly regulating gene expression related to blood cell formation.

Techniques to select and expand CD34+ cells have been developed for use in transplantation and gene therapy, showing promise for successful cell engraftment and targeted treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD34+ positive haemopoietic cells: biology and clinical applications. Holyoake, TL., Alcorn, MJ.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Positive stem cell selection--basic science. [2007]

2. Germany pubmed.ncbi.nlm.nih.gov

Expansion of blood CD34 positive cells: committed precursors expansion does not affect immature hematopoietic progenitors. [2017]

3. England pubmed.ncbi.nlm.nih.gov

Treatment of poor marrow graft function with allogeneic CD34+ cells immunoselected from G-CSF-mobilized peripheral blood progenitor cells of the marrow donor. [2007]

4. England pubmed.ncbi.nlm.nih.gov

Factors affecting the CD34+ cell yields from the second donations of healthy donors: The steady-state lymphocyte count is a good predictive factor. [2017]

5. England pubmed.ncbi.nlm.nih.gov

Clinical applications of CD34(+) peripheral blood progenitor cells (PBPC). [2005]

6. England pubmed.ncbi.nlm.nih.gov

Adverse reactions during stem cell infusion in children treated with autologous and allogeneic stem cell transplantation. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Toxicity related to autologous peripheral blood haematopoietic progenitor cell infusion is associated with number of granulocytes in graft, gender and diagnosis of multiple myeloma. [2011]

8. England pubmed.ncbi.nlm.nih.gov

Highly purified CD34+ cells isolated using magnetically activated cell selection provide rapid engraftment following high-dose chemotherapy in breast cancer patients. [2006]

9. England pubmed.ncbi.nlm.nih.gov

Positive selection of CD34+ cells by immunoadsorption: factors affecting the final yield and hematopoietic recovery in patients with hematological malignancies and solid tumors. [2019]

10. Brazil pubmed.ncbi.nlm.nih.gov

Adverse reactions on day zero of hematopoietic stem cell transplantation: integrative review. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

[Phenotypic differences between CD34 positive cells in various transplantation tissues]. [2006]

12. China pubmed.ncbi.nlm.nih.gov

[Hematopoietic reconstitution in early period after autologous and allogeneic peripheral blood stem cell transplantation]. [2017]

13. England pubmed.ncbi.nlm.nih.gov

CD34+ positive haemopoietic cells: biology and clinical applications. [2019]