Protocol - Sickle Cell Disease Stem Cell Source and Cell Manipulation

Description

This protocol uses existing medical records to document information about the stem cell donor, the doner’s relationship to the patient, the place in the body from which the stem cells were collected, human leukocyte antigen match or mismatch, and any gene therapy or other drug treatment administered to the stem cells before their transplantation in a patient with sickle cell disease. The first part of the protocol includes six questions from the Center for International Blood and Marrow Transplant Research CIBMTR Data Collection Form 2400 Pre-Transplant Essential Data (Pre-TED). The second part of the protocol includes questions from the Drug Product Case Report Form from the Cure Sickle Cell Disease Initiative (CureSCi) Common Data Element Project.

Specific Instructions

In Question 2 below, PBSC stands for peripheral blood stem cell.

Availability

Available

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Protocol

Donor Information for this HCT

(from Center for International Blood & Marrow Transplant Research form 2400)

1. Specify donor

[ ] Autologous

[ ] Allogenic, related

[ ] Allogenic, unrelated

2. Specify product type (check all that apply)

[ ] Bone marrow

[ ] PBSC

[ ] Single cord blood unit

[ ] Other product

Specify other product ___________________

3. Is the product genetically modified? (if autologous, go to the Drug Product Case Report Form below. If allogeneic related, go to question 4. If allogeneic unrelated, go to question 7.)

[ ] Yes

[ ] No

4. If allogenic, specify the related donor type

[ ] Syngeneic (monozygotic twin)

[ ] HLA-identical sibling (may include non-monozygotic twin)

[ ] HLA-matched other relative (does NOT include a haplo-identical donor)

[ ] HLA-mismatched relative

5. Specify the biological relationship of the donor to the recipient

[ ] Mother

[ ] Father

[ ] Child

[ ] Sibling

[ ] Fraternal twin

[ ] Maternal aunt

[ ] Maternal uncle

[ ] Maternal cousin

[ ] Paternal aunt

[ ] Paternal uncle

[ ] Paternal cousin

[ ] Grandparent

[ ] Grandchild

[ ] Other biological relative

Specify other biological relative:_______________

6. Degree of mismatch (related donors only)

[ ] HLA-mismatched 1 allele

[ ] HLA-mismatched ≥ 2 alleles (does not include haplo-identical donor)

7. Specify unrelated donor type

[ ] HLA matched unrelated

[ ] HLA mismatched unrelated

Drug Product CRF (only for Autologous Donor Products)

(from Cure Sickle Cell Disease Initiative Common Data Element (CureSCi CDE) Project)

Drug Product Starting Material:

[ ] Hematopoietic Progenitor Cell, Apheresis (HPC-A)

[ ] Hematopoietic Progenitor Cell, Marrow (HPC-M)

[ ] Hematopoietic Progenitor Cell, Cord Blood (HPC-C)

Manufacture Information

Date of Drug Product Manufacture__________________

[ ] Proportion of CD34+ cells _________

[ ] Total Colonies Formed: ______ per _______ cells

Expression of globin chain of interest:

[ ] Qualitative Assay: [ ] Positive [ ] Negative

[ ] Quantitative Assay: ___________

Were any additional drug product potency assays performed on drug product?

[ ] Yes [ ] No

If yes, describe and report result________________________________

Type of Modification:

[ ] Integrating Vector

[ ] Gene Editing Nuclease

[ ] Stem Cell Expansion

POPULATE SECTION A FOR INTEGRATING VECTOR CELL PRODUCT

POPULATE SECTION B FOR GENE EDITED CELL PRODUCT

Section A

Type of Integrating Vector: [ ] Retrovirus [ ] Lentivirus [ ] Other______________

[ ] Drug Product VCN______

[ ] Percentage of cells positive for integrating vector _________

[ ] Drug Product VCN/cell ________

Section B

Type of Editing: [ ] CRISPR-Cas 9 [ ] ZFN [ ] TALEN [ ] Cytosine Base Editing

[ ] Other______________

Mode of nuclease delivery: [ ] mRNA by EP [ ] RNP by EP [ ] AAV [ ] Other

gRNA target gene_________________ Mode of Delivery___________

Donor Template used? [ ] Yes [ ] No

If Yes, mode of delivery: [ ] ssODN [ ] AAV [ ] Other [ ] Drug Product:

On-target Indels______ Verified off-target indels_________

Conversion _______%

Personnel and Training Required

Personnel who are trained in performing medical record review

Equipment Needs

None

Requirements

Requirement Category	Required
Major equipment	No
Specialized training	No
Specialized requirements for biospecimen collection	No
Average time of greater than 15 minutes in an unaffected individual	No

Mode of Administration

Medical record abstraction

Lifestage

Infant, Toddler, Child, Adolescent, Adult, Senior, Pregnancy

Participants

All ages

Selection Rationale

The Sickle Cell Disease Curative Therapies Working Group selected questions from the Center for International Blood and Marrow Transplant Research (CIBMTR) and the Cure Sickle Cell Disease Initiative Common Data Element Project as the best standardized methodologies for collecting data on stem cell source and cell manipulation. CIBMTR forms, which are commonly used in stem cell transplantation research, were developed with the international transplant community to establish a standard set of data elements to be collected for all transplant recipients. Additionally, there are comprehensive Forms Instruction Manuals to help investigators complete the questions. The Cure Sickle Cell Initiative Drug Product Case Report Form was developed specifically for use in sickle cell disease and supplements the questions from CIBMTR.

Language

English

Standards

Standard	Name	ID	Source

Derived Variables

None

Process and Review

Not applicable.

Protocol Name from Source

Cure Sickle Cell Initiative (CureSCi) Drug Product Case Report Form and Center for International Blood and Marrow Transplant Research (CIBMTR) Form 2400 (R8.0) Pre-Transplant Essential Data, 2021

Source

Center for International Blood and Marrow Transplant Research. (2021, January). Pre-Transplant Essential Data (Pre-TED) Form (CIBMTR Form 2400; Revision 8.0), Questions 46–54. National Heart, Lung, and Blood Institute.

National Heart, Lung, and Blood Institute Cure Sickle Cell Disease Initiative Common Data Element (CDE) Project, Genetics/Assays Working Group, Transplant Conditioning Regimen Case Report Form. (2020). Transplant Conditioning Regimen Case Report Form.

General References

Lee, C. J., Savani, B. N., Mohty, M., Labopin, M., Ruggeri, A., Schmid, C., Baron, F., Esteve, J., Gorin, N. C., Giebel, S., Ciceri, F., & Nagler, A. (2017). Haploidentical hematopoietic cell transplantation for adult acute myeloid leukemia: A position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica, 102(11), 1810–1822.

Panch, S. R., Szymanski, J., Savani, B. N., & Stroncek, D. F. (2017). Sources of hematopoietic stem and progenitor cells and methods to optimize yields for clinical cell therapy. Biology of Blood and Marrow Transplantation, 23(8), 1241–1249.

Protocol ID

850501

Variables

Export Variables

Variable Name	Variable ID	Variable Description	dbGaP Mapping
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Any_Additional_Drug_Product_Potency_Assays_Performed
	PX850501140100	Were any additional drug product potency more assays performed on drug product show less	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Any_Additional_Drug_Product_Potency_Assays_Performed_If_Yes_Describe_Report_Result
	PX850501140200	Were any additional drug product potency more assays performed on drug product: If yes, describe and report result show less	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Conversion
	PX850501230300	Conversion	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Date_Drug_Product_Manufacture
	PX850501090000	Date of drug product manufacture	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Degree_Mismatch_Related_Donors_Only
	PX850501060000	Degree of mismatch for related donors	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Donor_Template_Used
	PX850501220100	Donor Template Used?	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Donor_Template_Used_Yes
	PX850501220200	Donor Template Used? If yes, mode of delivery	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Drug_Product_Starting_Material
	PX850501080000	Drug product starting material	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Drug_Product_VCN
	PX850501170000	Drug product VCN	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Drug_Product_VCN_Cell
	PX850501190000	Drug product VCN/cell	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Expression_Globin_Chain_Interest_Qualitative_Assay
	PX850501120000	Expression of globin chain of interest: more Qualitative Assay show less	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Expression_Globin_Chain_Interest_Quantitative_Assay
	PX850501130000	Expression of globin chain of interest: more Quantitative Assay show less	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Genetically_Modified
	PX850501030000	Is the product genetically modified?	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Genetically_Modified_Allogenic
	PX850501040000	Is the product genetically modified? more Allogenic: Specify related donor type show less	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Mode_Nuclease_Delivery
	PX850501210100	Mode of nuclease delivery	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Mode_Nuclease_Delivery_GRNA_Target_Gene
	PX850501210200	Mode of nuclease delivery: gRNA target gene	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Mode_Nuclease_Delivery_Mode_Delivery
	PX850501210300	Mode of nuclease delivery: Mode of delivery	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Off_Target_Indels
	PX850501230200	Off-target Indels	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_On_Target_Indels
	PX850501230100	On-target Indels	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Percentage_Cells_Positive_Integrating_Factor
	PX850501180000	Percentage of cells positive for integrating more factor show less	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Proportion_CD34_Cells
	PX850501100000	Proportion of CD34+ Cells	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Specify_Donor
	PX850501010000	Specify donor	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Specify_Donor_Relationship_Recipient
	PX850501050100	Specify donor relationship to the recipient	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Specify_Donor_Relationship_Recipient_Other_Biological_Relative
	PX850501050200	Specify donor relationship to the recipient: more Other biological relative - Specity other biological relative: show less	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Specify_Product_Type
	PX850501020100	Specify product type (check all that apply)	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Specify_Product_Type_Other
	PX850501020200	Specify product type (check all that apply): more Other product - Specify other product: show less	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Specify_Unrelated_Donor_Type
	PX850501070000	Specify unrelated donor type	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Total_Colonies_Formed
	PX850501110100	Total Colonies Formed	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Total_Colonies_Formed_Rate
	PX850501110200	Total Colonies Formed (rate)	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Type_Editing
	PX850501200100	Type of editing	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Type_Editing_Other
	PX850501200200	Type of editing: Other	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Type_Integrating_Vector
	PX850501160100	Type of integrating factor	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Type_Integrating_Vector_Other
	PX850501160200	Type of integrating factor: Other	N/A
PX850501_Sickle_Cell_Disease_Stem_Cell_Source_Manipulation_Type_Modification
	PX850501150000	Type of modification	N/A

SCD Curative Therapies

Measure Name

Sickle Cell Disease Stem Cell Source

Release Date

August 16, 2021

Definition

The stem cells used for a transplant may come from a donor either related or unrelated to the patient (allogeneic transplant) or from the patient’s own body (autologous transplant). Stem cells may also be collected from different sources, including directly from the bone marrow, from peripherally mobilized blood, or from umbilical cord blood. Before being used for transplantation, stem cells may be manipulated to further purify a specific cell population (in allogeneic transplants) or for use in gene therapy (including gene editing and gene addition in autologous transplants).

Purpose

The stem cell donor type, source type, and type of manipulation (if any) influence the outcome of a stem cell transplant for a patient with sickle cell disease, including the quantity of stem cells, speed of engraftment, risk of graft rejection, number of CD34+ cells, risk of graft versus host disease, and overall success or failure of the transplant to treat sickle cell disease.

Keywords

sickle cell disease, sickle cell curative therapies, stem cell, bone marrow transplant, gene therapy, stem cell donor type, allogenic transplant, autologous transplant, Center for International Blood and Marrow Transplant Research, CIBMTR

Measure Protocols

Protocol ID	Protocol Name
850501	Sickle Cell Disease Stem Cell Source and Cell Manipulation

Publications

There are no publications listed for this protocol.