Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SUMMARY: OBJECTIVE: In a significant proportion of patients with hematologic malignancies (5-30%) poor mobilization of hematopoietic stem cells (HSC) is observed. This compromises the application of effective and potentially curative high-dose chemotherapy (HDC) treatment. CASE REPORT: Here we report the case of a 38-year-old female patient who was treated for recurrent follicular B-cell non-Hodgkin's lymphoma grade III. In this patient, we failed twice to mobilize stem cells using chemotherapy followed by granulocyte-colony stimulating factor (G-CSF). Recently a new chemokine receptor CXCR4 antagonist, AMD3100 (plerixafor), was introduced which can be combined with G-CSF mobilization and has been reported to increase the number of harvested stem cells significantly. Using this protocol, we were able to harvest a HSC product. This product was transplanted 3 weeks after the harvest (after HDC), and the patient had an uncomplicated recovery of granulopoiesis (day 11 after transplantation of autologous HSC). CONCLUSION: Plerixafor has the potency to become an important tool in mobilizing HSC, especially in those patients in whom HSC cannot be mobilized by the combination of G-CSF and chemotherapy alone.
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PMID:Turning CD34 Non-Mobilizers into Mobilizers: A Case Report Involving Plerixafor (AMD3100). 2107 51

Autologous hematopoietic stem cell (HSC) transplantation is an important therapeutic option for patients with non-Hodgkin's lymphoma and multiple myeloma. The primary source of HSC is from the peripheral blood which requires mobilization from the bone marrow. Current mobilization regimens include cytokines such as G-CSF and/or chemotherapy. However not all patients mobilize enough HSC to proceed to transplant. The chemokine receptor CXCR4 and its ligand CXCL12 are an integral part of the mechanism of HSC retention in the bone marrow niche. The discovery of plerixafor, a selective inhibitor of CXCR4, has provided a new additional means of mobilizing HSC for autologous transplantation. Plerixafor consists of two cyclam rings with a phenylenebis(methylene) linker. It inhibits CXCL12 binding to CXCR4 and subsequent downstream events including chemotaxis. The molecular interactions of plerixafor have been defined indicating a unique binding mode to CXCR4. Plerixafor rapidly mobilizes HSC within hours compared with the multi-day treatment required by G-CSF in mouse, dog and non-human primate. The mobilized cells once transplanted are capable of timely and endurable engraftment. Additionally CXCR4 has been implicated in the pathology of HIV, inflammatory disease and cancer and the pharmacology of plerixafor in various disease models is described.
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PMID:Physiology and pharmacology of plerixafor. 2417 72