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Liz Higgins - Haematology Association of Ireland

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AutologousPeripheral<br />

Blood Stem Cell Harvest.<br />

<strong>Liz</strong> <strong>Higgins</strong><br />

BMT Co-ordinator<br />

St James’s Hospital, Dublin


National BMT/PBSCT<br />

Unit<br />

Allogenic<br />

Autologous PBSCT –<br />

GUH<br />

SVH<br />

Shared Care SJH - AMNCH,<br />

Beaumont, Mater hospitals.


PBSCH<br />

2008 71<br />

2009 75<br />

2010 54 to date


TEAM<br />

Referring Consultant<br />

Referring CNS<br />

Apheresis Team<br />

Cryobiology Team<br />

CNM<br />

Stem cell Transplant Co-Ordinators


PBSCT<br />

PBSCT involves eliminating an<br />

individual’s bone marrow stem cells.<br />

They are then replaced with bone<br />

marrow stem cells either from another<br />

individual or with a previously<br />

harvested portion <strong>of</strong> the individuals<br />

own bone marrow or peripheral blood<br />

stem cells.


Reasons for PBSCT<br />

Defective marrow function e.G. Aplastic<br />

anaemia, myelodysplasia, severe combined immune<br />

deficiency, sickle cell disease, and other benign<br />

inherited disorders<br />

Diseased marrow function e.G. Acute and<br />

chronic leukaemia<br />

To facilitate high dose therapy in<br />

other malignant conditions e.G.<br />

Lymphoma, testicular cancer, Multiple Myeloma.


Cancers treated by<br />

Autologous PBSCT<br />

Hodgkin,s disease<br />

Non Hodgkin's Lymphoma<br />

Chronic Myeloid Leukaemia<br />

Acute Myeloid Leukaemia<br />

Acute Lymphocytic Leukaemia<br />

Multiple Myeloma<br />

Testicular CA<br />

Ewing's Sarcoma.


Stem Cell<br />

Red Cell or White Cell or<br />

Platelet<br />

Once the ‘decision’ is made it is<br />

probably irreversible


Sources <strong>of</strong> Bone Marrow<br />

Stem Cells<br />

Bone marrow (BM) - aspirated from<br />

the posterior iliac crests under GA,<br />

usually 800-1200mls in volume<br />

Peripheral blood stem cells<br />

(PBSC) - following the administration<br />

<strong>of</strong> growth colony stimulating factor (G-<br />

CSF) + / - Chemotherapy


Autologous rescue involves two<br />

processes.<br />

PBSCH/ BMH<br />

PBSCT/ BMT


PBSCH<br />

COMMISSION DIRECTIVE 2006/17/EC<br />

<strong>of</strong> 8 February 2006<br />

implementing Directive 2004/23/EC <strong>of</strong><br />

the European Parliament and <strong>of</strong> the<br />

Council as regards<br />

certain technical requirements for the<br />

donation, procurement and testing <strong>of</strong><br />

human tissues and cells


Storage<br />

Liquid Nitrogen<br />

Stored in Vapour phase<br />

- 190 C<br />

15 Years


PBSC Mobilisation<br />

Initial Review<br />

FBC<br />

RLB Pr<strong>of</strong>ile<br />

Coagulation<br />

Blood group<br />

G&H<br />

Disease markers<br />

Virology – Hepatitis<br />

B,C; HIV 1&2; HTLV<br />

1&2; Syphilis<br />

Consider venous<br />

access –<br />

peripheral/central<br />

Medical assessment<br />

Nursing Assessment<br />

Counselling<br />

CXR/ ECG/ ECHO<br />

Consent<br />

Correspondence


Mobilisation Regimens<br />

G-CSF 10mcg/kg X 4 days<br />

IEV<br />

ICE<br />

Cyclophosphamide 2grms / M 2<br />

Ivac<br />

Dhap<br />

ESHAP<br />

Taxol / Ifos x 2<br />

VIDE


Cyclophosphamide<br />

2g/m 2<br />

Chemo on Monday<br />

Commence G-CSF (10mcg/Kg<br />

Tuesday)<br />

CD34 Count from day 8<br />

Leucapheresis day 8-10


GSCF ( Neupogen)<br />

10Mcg / kg Round up.<br />

Commence on Saturday.<br />

CD34 Count Tuesday +/- Gcsf<br />

PBSCH


ICE<br />

Etoposide 10mg/m 2 Day 1,2,3.,<br />

Carboplatin AUC 5 Day 2, Ifosfamide<br />

5000mg/m 2 24 hour infusion Day 2<br />

Neupogen 5 mcg/kg commence day 6<br />

Commence ICE on Thursday<br />

PBSCH 12-14 days Post<br />

Usually Wed for harvest


IEV / DHAP/ IVAC<br />

Wednesday<br />

PBSCH day 12-14


Eshap<br />

Commence Tuesday<br />

Day 12-14


Aphoresis<br />

Pending Peripheral CD34 Count x<br />

10 3 /ml<br />

(EDTA sample in lab for 8am)<br />

Monitored daily<br />

1-3 Days<br />

4-5 Hours<br />

Inpatient or Transfer as day patient


Apheresis guidelines


Pre harvest procedure<br />

Neutropenic<br />

Antibiotic therapy<br />

Throbcytopenia<br />

Platelet count > 30 for procedure<br />

Anaemia.<br />

HB > 8 for procedure<br />

Anticoagulation Therapy<br />

Drugs


COBE


Failure to Mobilise.<br />

2009 11 Patients failed to mobilise.


Autologous HSCT in<br />

multiple myeloma and lymphoma<br />

It is generally accepted that patients must collect a minimum <strong>of</strong> 2 x 10 6<br />

CD34+ cells/kg during apheresis to proceed with high dose<br />

chemotherapy and stem cell rescue.<br />

Patients who fail to collect this number <strong>of</strong> cells are usually considered<br />

mobilisation failures<br />

Current clinical practice involves remobilizing these patients with<br />

existing G-CSF or chemotherapy plus G-CSF regimens<br />

Menu


Risk factors for<br />

poor or failed mobilisation<br />

Advanced age<br />

Bone marrow involvement by tumour<br />

Extensive radiation to marrow sites<br />

Extensive prior therapy<br />

Mobilisation with G-CSF alone<br />

Previous treatment with alkylating agents<br />

Prior fludarabine or lenalidomide treatment<br />

General physical status<br />

Menu


Indication<br />

Plerixafor is indicated in combination with G-CSF to<br />

enhance mobilisation <strong>of</strong> haematopoietic stem cells to the<br />

peripheral blood for collection and subsequent autologous<br />

transplantation in patients with lymphoma and multiple<br />

myeloma whose cells mobilise poorly


Plerixafor: a first in class<br />

stem cell mobilising agent<br />

Structural formula <strong>of</strong> plerixafor 16<br />

Plerixafor is a first in class CXCR4 antagonist that mobilises stem<br />

cells from the bone marrow, increasing their number in peripheral<br />

blood<br />

Its mode <strong>of</strong> action is to block the chemokine receptor 4 (CXCR4, found<br />

on stems cells), preventing binding.<br />

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Mechanism <strong>of</strong> action <strong>of</strong> Plerixafor<br />

Plerixafor blocks the CXCR4–SDF-1α interaction, releasing stem cells from<br />

the bone marrow into the circulating blood.<br />

Menu


The recommended dose <strong>of</strong> Plerixafor is 0.24mg/kg body weight/day. It should<br />

be administered by subcutaneous injection at a time that will allow an interval<br />

between dosing and the initiation <strong>of</strong> apheresis that is a minimum <strong>of</strong> 10 hours<br />

and a maximum <strong>of</strong> 11 hours.<br />

Gcsf at part <strong>of</strong> standard care – administered in the morning , and on the days <strong>of</strong><br />

apheresis, at least one hour prior to the initiation <strong>of</strong> apheresis.<br />

Plerixafor 10pm<br />

Gcsf 7am<br />

Apheresis 8.30am<br />

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Plerixafor increases predictability <strong>of</strong><br />

apheresis yield and timing<br />

Menu


Numbers<br />

14 patients<br />

7 MM<br />

7 Lymphoma<br />

3 failures ( Lymphoma Pts)

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