Type of product
TNC/kg body weight of recipient
CD34 + cell/kg body weight of recipient
Bone marrow
> 2 × 108
Peripheral blood stem cells
> 2 × 108
> 3 × 106
Double cord blood—each unit
> 2 × 107
Single cord blood—5/6 match
> 2.5 × 107
Single cord blood—4/6 match
> 5 × 107
T cell depleted
> 5 × 106
Haploidentical
> 5 × 106
10.
Myelotoxin exposure (ganciclovir, ACE inhibitors, trimethoprim/sulfamethoxazole, vancomycin, linezolid, H2 blockers, etc.)
11.
Damaged marrow microenvironment
12.
Allosensitization
30.5 Diagnosis
1.
Peripheral blood cell counts. Previous studies have shown that a leukocyte count of < 200/mm3 on day + 16 post-HSCT is a strong predictor of subsequent primary graft failure.
2.
Bone marrow aspirate and biopsy
a.
In both autologous and allogeneic recipients, bone marrow studies demonstrate a hypocellular marrow with no identifiable myeloid, erythroid, or megakaryocytic precursors.
3.
Chimerism studies
a.
Fluorescent in situ hybridization (FISH)/cytogenetics for sex-mismatched recipient/donor
b.
Variable number of tandem repeats (VNTR) for sex-matched recipient/donor. These studies require pre-HSCT storage of DNA material (blood) from both donor and recipient.
4.
Disease-specific double-fusion products (i.e., BCR/abl PCR)
5.
CMV PCR, HHV6 PCR, Parvovirus PCR
6.
Ensure nutrients important to hematopoiesis are adequate
a.
Methylmalonic acid, homocysteine, and copper levels
b.
Thyroid function studies
30.6 Treatment
1.
Autologous HSCT recipients
a.
Hematopoietic growth factors (e.g., filgrastim +/− sargramostim) are more successful in treating hematopoietic failure than graft rejection.
b.
Consider dose escalated filgrastim at doses of 10 mcg/kg/day or 5 mcg/kg BID.
c.
Stem cell boost without additional conditioning provided the patient has additional stem cells cryopreserved.
d.
Consider agents that may stimulate hematopoietic stem cells.
i.
Trilineage hematopoietic responses were demonstrated in patients receiving eltrombopag (Promacta®), a thrombopoietin receptor agonist, for severe aplastic anemia.
ii.
Androgenic steroids (i.e., danazol) are early in studies in post-HSCT marrow failure.
2.
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Allogeneic HSCT recipients
a.
Hematopoietic growth factors (e.g., filgrastim +/− sargramostim) are more successful in treating hematopoietic failure than graft rejection.
i.
Consider dose escalated filgrastim 10 mcg/kg/day versus 5 mcg/kg BID.
b.
Stem cell boost +/− additional pre-infusion conditioning agents based on availability of original donor/product and assessment of the degree of host versus donor CD33 + and CD3 + chimerisms.
c.
Utilization of a different donor (i.e., cord blood or haploidentical donor) after fludarabine-based conditioning +/− TBI for engraftment failure shows promise.
d.
Augmentation of immunosuppression can be considered, particularly in the setting of decreasing donor chimerism.
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