Board Prep: Introduction to Stem Cell Collection and Transplant

Stem cell collection sits at the intersection of hematology, immunology, and procedural medicine. It’s conceptually simple — collect enough hematopoietic stem cells to reconstitute marrow — but operationally complex, with decisions at every step that affect engraftment, toxicity, and long-term outcomes.

This post walks through stem cell collection from a practical, systems-level perspective: what we collect, where it comes from, how we mobilize it, and what determines whether a transplant succeeds.

The Big Picture: What Are We Collecting?

At the center of stem cell transplantation are hematopoietic stem cells (HSCs) — most commonly identified clinically as CD34-positive cells. These cells are capable of:

• Self-renewal

• Differentiation into all mature blood lineages

  
  

Clinically, we collect them for three main purposes:

• Autologous transplant, where patients receive their own cells back after myeloablative therapy

• Allogeneic transplant, where donor cells replace a recipient’s marrow

• Marrow rescue following intensive chemotherapy

  
  

While multiple sources exist, modern practice overwhelmingly favors peripheral blood collection.

Where Stem Cells Come From

Peripheral Blood

Peripheral blood stem cells are now the dominant source for both autologous and allogeneic transplants. They:

• Yield higher CD34+ cell counts

• Engraft faster than bone marrow

• Are collected via apheresis rather than surgery

  
  

The tradeoff, particularly in the allogeneic setting, is a higher risk of graft-versus-host disease (GVHD).

Bone Marrow

Bone marrow harvests are obtained directly from the iliac crests under anesthesia. Compared with peripheral collections, they:

• Require invasive access

• Contain more red blood cell contamination

• Carry higher risk of contamination with skin flora

  
  

They are used less frequently but remain relevant in specific clinical contexts.

Cord Blood

Cord blood is largely peripheral to apheresis practice but remains board-relevant. It is:

• Cryopreserved and banked long-term

• More tolerant of HLA mismatch

• Limited by lower total cell dose, sometimes requiring multiple units or ex vivo expansion

  
  

Mobilization: Getting Stem Cells Into the Blood

Under normal conditions, hematopoietic progenitor cells reside in the bone marrow niche, where adhesion molecules and chemokine gradients keep them anchored and quiescent.

Mobilization disrupts that relationship.

Key mechanisms include:

• CXCR4–CXCL12 (SDF-1α) signaling, which tethers stem cells to marrow stroma

• Soluble factors such as stem cell factor

• Proteases and neurotransmitter-mediated signals

  
  

The most commonly used mobilizing agent is G-CSF, which indirectly alters the marrow microenvironment and increases circulating CD34+ cells.

Plerixafor (AMD3100, Mozobil) works differently: it directly inhibits CXCR4, rapidly releasing stem cells into the peripheral circulation. This is particularly useful in poor mobilizers.

How We Collect Stem Cells

Apheresis

Peripheral blood stem cells are collected via leukapheresis, using continuous-flow cell separators. The procedure:

• Processes large blood volumes

• Uses ACD-A as the anticoagulant

• Selectively collects mononuclear cells enriched for CD34+ cells

  
  

This is the most common and operationally efficient collection method.

Bone Marrow Harvest

Bone marrow collection involves multiple passes through skin and cortical bone. Compared with apheresis, it:

• Has higher contamination risk

• Produces products with more RBCs

• Carries procedural risks such as bleeding and post-procedure anemia

  
  

How Much Is Enough? Target Cell Dose

Cell dose matters — both for engraftment speed and downstream complications.

• Autologous transplant

  • Minimum effective dose: ~2 × 10⁶ CD34+ cells/kg

  • Optimal dose: 4–6 × 10⁶ CD34+ cells/kg

• Allogeneic transplant

  • Similar target range

  • Higher doses improve engraftment but increase GVHD risk

    
    

Collection strategies often balance donor safety, collection efficiency, and the marginal benefit of additional cells.

Complications of Stem Cell Collection

Citrate Toxicity (Most Common)

ACD-A chelates calcium, leading to hypocalcemia. Symptoms range from:

• Perioral tingling and paresthesias

• Tetany

• Cardiac arrhythmias in severe cases

  
  

Management includes oral or IV calcium supplementation and slowing the collection rate.

Vascular Access Issues

Central venous catheters carry risks of:

• Infection

• Thrombosis

• Bleeding

  
  

Donor-Specific Issues

Allogeneic donors may experience G-CSF-related side effects, most commonly bone pain and headache. Donor safety always takes precedence over collection yield.

Bone Marrow Harvest Complications

These include local site pain, bruising, hematoma formation, and anemia.

Autologous vs Allogeneic Collection: Why the Difference Matters

Autologous transplants avoid GVHD but lack graft-versus-tumor effects. Allogeneic transplants introduce immunologic risk — but also therapeutic benefit.

This balance drives donor selection, conditioning regimens, and post-transplant monitoring.

Infectious Disease Testing and Product Handling

All stem cell products require infectious disease screening, including:

• HIV

• HBV

• HCV

• HTLV

• Syphilis

  
  

Product handling differs by transplant type:

• Autologous products are typically cryopreserved

• Allogeneic products may be infused fresh or frozen

  
  

Cryopreservation Basics

• DMSO is the most common cryoprotectant

• Controlled-rate freezing precisely regulates temperature to prevent intracellular ice crystal formation

• Passive freezing uses insulated containers and −80 °C storage but offers less control

  
  

Engraftment: The Endpoints Everyone Cares About

Boards — and clinicians — care deeply about engraftment definitions:

• Neutrophil engraftment: ANC > 500 for 3 consecutive days

• Platelet engraftment: Platelets > 20,000 without transfusion support for 7 days

  
  

These metrics anchor post-transplant monitoring and outcome reporting.

Consolidated Board Pearls

Stem Cell Sources

• Which source has the most CD34+ cells? → Peripheral blood

• Highest GVHD risk? → Peripheral blood

• Faster engraftment than marrow? → Yes

  
  

Mobilization

• Mechanism of plerixafor? → CXCR4 inhibition

• Most commonly used mobilizing agent? → G-CSF

  
  

Collection

• Highest contamination risk with skin commensals? → Bone marrow harvest

• Most common collection method? → Apheresis

  
  

Target Dose

• Minimum effective dose? → 2 × 10⁶ CD34+ cells/kg

• Benefit of higher dose? → Faster engraftment

• Risk of higher dose? → GVHD

  
  

Apheresis Complications

• Most common anticoagulant? → ACD-A

• Mechanism? → Calcium chelation

• Most common side effect? → Hypocalcemia

• Treatment? → Calcium supplementation

• Most common G-CSF side effect? → Bone pain

  
  

Autologous vs Allogeneic

• Risk of allogeneic transplant? → GVHD

• Benefit? → Graft-versus-tumor effect

  
  

Product Handling

• Most common cryoprotectant? → DMSO

• Why controlled-rate freezing? → Prevents intracellular ice crystals

  
  

Engraftment

• Neutrophils: ANC > 500 for 3 days

• Platelets: >20k without transfusion for 7 days