High-dose chemotherapy with autologous stem-cell transplantation asct is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony—stimulating factor g - csf ; however, some patients are not able to be mobilized with chemotherapy and g - csf , and such patients could be at higher risk of failing mobilization.
Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0. The main purpose of the present report was to evaluate the most current evidence on the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct for patients in Ontario so as to make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to this intervention.
The medline and embase databases were systematically searched for evidence from January to March , and the best available evidence was used to draft recommendations relevant to the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct. High-dose chemotherapy with autologous stem-cell transplantation asct is an accepted part of standard therapy for a variety of hematologic malignancies, including non-Hodgkin nhl and Hodgkin lymphoma hl , multiple myeloma mm , and germ-cell tumours.
The benefits of transplantation include improvement in disease control and can include an improved overall survival rate. In some situations, asct is potentially curative. A necessary step in the process of treating patients with high-dose chemotherapy is the ability to mobilize, collect, and cryopreserve autologous stem cells. Although a variety of protocols are available, stem-cell mobilization is usually performed using granulocyte colony—stimulating factor g - csf , often with the addition of chemotherapy for example, high-dose cyclophosphamide.
In some clinical scenarios, patients are not able to undergo mobilization with chemotherapy and g - csf , and such patients can be at higher risk of failing mobilization. Other risk factors for failing mobilization include prior treatment with multiple lines of chemotherapy or purine analogues, radiation to bone marrow—containing areas, and patient age; however, those factors remain poorly defined for the most part and largely consensus-driven 1.
Plerixafor is absorbed quickly after a subcutaneous injection and, at the recommended dose of 0. Dose adjustments are not needed for patients with hepatic or renal insufficiency, and in general, the agent is well tolerated.
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In December , Health Canada approval was granted for the use of plerixafor with g - csf in stem-cell mobilization for patients with nhl or myeloma. To make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to intervention with plerixafor, the Working Group of the Stem Cell Transplant Steering Committee developed the present recommendation report.
Based on the objectives of the guideline, the members of the Working Group derived the research questions as outlined later in the report. This recommendation report, produced by the Program in Evidence-Based Care pebc and approved by the Stem Cell Transplant Steering Committee of Cancer Care Ontario, was developed through a systematic review of the available evidence using the methods of the practice guidelines development cycle 2 , 3.
This evidence review was conducted in 3 planned stages, including a search for existing guidelines followed by a search for systematic reviews and primary literature. Before any search for systematic reviews or primary literature, an electronic search for existing guidelines concerning the efficacy of plerixafor was conducted using the electronic databases medline Ovid and embase Ovid and the Standards and Guidelines Evidence sage directory of cancer guidelines. The goal was to identify existing guidelines for adaptation or endorsement so as to avoid duplication of guideline development efforts across jurisdictions.
Only guidelines published in English and after were considered and evaluated for quality using the agree ii instrument 4. Any systematic reviews identified were assessed for quality using amstar 5 ; the results of the amstar assessment were used to determine the inclusion of existing systematic reviews as part of the evidence base.
Assuming that no existing guidelines or systematic reviews were identified, a systematic review of the primary literature was also planned. If a suitable guideline or systematic review had been found, a systematic review of the primary literature would be conducted from the date of the reported search, solely to update the evidence from the existing guidelines or systematic reviews.
In April , the medline Ovid; through 18 April and embase Ovid; through Week 16, databases were searched for primary literature; the search was updated in March The search strategy included a logical combination of terms for the condition stem-cell transplantation , the intervention plerixafor , and studies of interest systematic reviews, clinical trials, nonrandomized studies with an appropriate control group. Relevant articles were reviewed by 2 reviewers CTK, NPV , and the reference lists from those sources were searched for additional trials.
A data audit procedure was conducted by an independent individual Kristy Yiu to verify the accuracy of the information obtained from the included studies. Twenty-two studies assessing the efficacy and safety of plerixafor for autologous stem-cell mobilization and transplantation were retained: two randomized controlled trials rct s 6 , 7 , five nonrandomized controlled trials 8 — 12 , three retrospective cohort studies with a contemporaneous control arm 13 — 15 , and twelve single-arm studies 16 — Quality was assessed according to the criteria described in the Methods section.
Table i provides details about patient selection criteria, peripheral blood stem-cell mobilization regimen, sample size, and reported outcomes. The two rct s reported by DiPersio et al. In the lymphoma study 6 , patients were randomized , but other details were not reported. In the myeloma study 7 , patients were stratified by study centre, baseline platelet count, and type of transplantation planned. The five nonrandomized controlled trials 8 — 12 included fully described the inclusion and exclusion criteria, mobilization protocol, and outcomes of interest.
Four of the studies compared outcomes with matched historical controls mobilized using a therapy that did not include plerixafor 8 , 9 , 11 , The twelve single-arm trials 16 — 27 were included in the review to inform recommendations both for patients failing mobilization before asct and for patients failing a prior mobilization attempt. In all those studies, the patients were fully described and were representative of the population of interest.
In all studies, the mobilization regimen was consistent with the regimen that would be used in Ontario clinical practice. Eight of the studies 17 , 18 , 20 — 23 , 26 , 28 included patients enrolled in a European compassionate-use program cup for patients who had previously failed conventional mobilization attempts. The inclusion and exclusion criteria were fully described for all those studies.
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The remaining three trials were independent studies conducted in education centres in Finland 24 and the United States 25 , Some studies reported the number and proportion of patients who proceeded to asct and who survived to the month follow-up. Overall, the quality assessment found all of the foregoing plerixafor trials to be of acceptable quality given the nature of their study designs.
Advanced search. Home Journals Why publish with us? Therefore, we evaluated the efficacy and safety of stem cell mobilization using intermediate doses of VP and high doses of CY in patients with MM.
- SDF-1 Effect on Hematopoietic Progenitor and Stem Cell Mobilization: R&D Systems.
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We retrospectively analyzed the medical records of patients diagnosed with MM who underwent stem cell mobilization between February and February at Chonnam National University Hwasun Hospital. We excluded patients who mobilized with G-CSF alone. Following these exclusions, a total of patients were included in this study. The International Myeloma Working Group uniform response criteria were used to assess the response to treatment [ 16 ].
The duration of hospitalization was defined as the number of days from the initiation of the conditioning regimen for ASCT to the day of discharge. Discrete and continuous variables were evaluated using the chi-square test and a Mann-Whitney U -test, respectively. The PFS was calculated from the day of transplantation to disease progression or death from any cause. Overall survival OS was calculated from the day of transplantation to the day of death from any cause. All statistical analyses were performed using SPSS software ver. Sixty-five patients Overall, the patients had similar disease characteristics such as ISS stage, immunoglobulin subtype, serum levels of lactate dehydrogenase LDH and creatinine, baseline levels of hemoglobin, and platelet counts.
Patients had received a median of one range, 1—3 prior treatment regimen before stem cell mobilization.
Nine patients The frontline treatment differed slightly between the two groups, with more patients being treated with a bortezomib-containing regimen in the VP group The median time from the first treatment to mobilization was shorter in the VP group than the CY group 3. The number of patients who received spinal radiotherapy was similar in both groups Fewer patients failed stem cell collection in the VP mobilization group than in the CY mobilization group 1. In the VP group, only one patient showed mobilization failure and also failed to provide a sufficient amount of stem cells in a subsequent mobilization attempt using plerixafor.
Among the seven patients who had mobilization failure with CY, three decided not to pursue ASCT, one received a bone marrow harvest, one underwent a repeated mobilization procedure with CY, and two received a second mobilization procedure with G-CSF only. As a result, patients were transplanted with a larger number of hematopoietic stem cells in the VP group than in the CY group Fifty-seven patients Most patients in the CY group received a high-dose melphalan conditioning regimen The median number of patients requiring platelet transfusion support during the transplantation period was fewer in the VP group 2 vs.
There were no significant differences between the two groups with respect to the median time to neutrophil engraftment. After a median follow-up time of Kaplan-Meier survival curves for progression free survival a and overall survival b in all patients. More patients in the CY group required supportive transfusion during the mobilization period, which is defined as the time between the first day of mobilization chemotherapy infusion and the last day of collection.
In all, 42 In addition, 47 Non-hematological toxicities occurred in Following mobilization chemotherapy, the most common non-hematological toxicity was infection. The overall incidence of infection after mobilization was higher in the CY group All patients who developed severe infections were successfully treated with broad spectrum antibiotics, which resulted in no patient deaths in either group.
Other non-hematological toxicities included gastrointestinal and hepatotoxicity.
Advances in stem cell mobilization. - Abstract - Europe PMC
One patient showed a mild hypersensitive reaction, including pruritus and facial swelling, after infusion of CY, which was resolved by chlorpheniramine injection. Two patients complained of grade 1 or 2 nausea and vomiting, and were also relieved of these symptoms after supportive care.
There was no treatment-related mortality during the mobilization period in either patient group. There is little consensus on the most appropriate regimen for stem cell mobilization for MM. The addition of plerixafor, a chemokine receptor type 4 inhibitor, to G-CSF has shown good mobilization results in many studies and has ignited the pursuit to improve mobilization regimens [ 17 , 18 , 19 ]. However, there is a lack of research examining both the long-term efficacy and adverse effects of plerixafor.
In addition, it is not clearly defined when plerixafor should be used as a primary mobilization regimen, nor what type of patients should be targeted.
SDF-1 Effect on Hematopoietic Progenitor and Stem Cell Mobilization
Another important factor is that plerixafor is expensive and many countries do not subsidize its use, which may impose a financial burden on many patients. As conventional chemo-mobilization is still expected to play a large role in ASCT, alternatives to plerixafor are highly desirable. Improved mobilization using VP is meaningful in this sense, as it is a promising candidate as a plerixafor replacement.
In patients mobilized with VP, many more stem cells could be collected safely over fewer days of apheresis compared to CY mobilization. The number of patients for whom an adequate amount of stem cells could not be collected was also lower in the VP group. The time from the first treatment to mobilization was also longer in the CY mobilization group than the VP mobilization group 4. We surmise that these differences are due to disparities in the induction regimen schedule between the two groups.
The majority of induction regimens at our institution follow a day schedule; however, some regimens have a day schedule.