Cost‐effectiveness of hematopoietic stem cell mobilization strategies including plerixafor in multiple myeloma and lymphoma patients

Peripheral blood stem cells (PBSCs) are preferred source of hematopoietic stem cells for autologous transplantation. Mobilization of PBSCs using chemotherapy and/or granulocyte colony‐stimulating factor (G‐CSF) however fails in around 20%. Combining G‐CSF with plerixafor increases the mobilizations success. We compared cost‐effectiveness of following schemes: the use of plerixafor “on demand” (POD) during the first mobilization in all patients with inadequate response, the remobilization with plerixafor following failure of the first standard mobilization (SSP), and the standard (re)mobilization scheme without plerixafor (SSNP). Decision tree models populated with data from a first‐of‐a‐kind patient registry in six Czech centers (n = 93) were built to compare clinical benefits and direct costs from the payer's perspective. The success rates and costs for POD, SSP and SSNP mobilizations were; 94.9%, $7,197; 94.7%, $8,049; 84.7%, $5,991, respectively. The direct cost per successfully treated patient was $7,586, $8,501, and $7,077, respectively. The cost of re‐mobilization of a poor mobilizer was $5,808 with G‐CSF only and $16,755 if plerixafor was added. The total cost of plerixafor “on‐demand” in the sub‐cohort of poor mobilizers was $17,120. Generally, plerixafor improves the mobilization success by 10% and allows an additional patient to be successfully mobilized for incremental $11,803. Plerixafor is better and cheaper if used “on demand” than within a subsequent remobilization. J. Clin. Apheresis 28:395–403, 2013. © 2013 Wiley Periodicals, Inc.     

Peripheral blood stem cell mobilization in multiple myeloma patients treat in the novel therapy‐era with plerixafor and G‐CSF has superior efficacy but significantly higher costs compared to mobilization with low‐dose cyclophosphamide and G‐CSF

Studies comparing the efficacy and cost of peripheral blood stem and progenitor cells mobilization with low‐dose cyclophosphamide (LD‐CY) and granulocyte‐colony stimulating factor (G‐CSF) against plerixafor and G‐CSF, in multiple myeloma (MM) patients treated in the novel therapy‐era are not available. Herein, we report mobilization outcomes of 107 patients who underwent transplantation within 1‐year of starting induction chemotherapy with novel agents. Patients undergoing mobilization with LD‐CY (1.5 gm/m²) and G‐CSF (n = 74) were compared against patients receiving plerixafor and G‐CSF (n = 33). Compared to plerixafor, LD‐CY was associated with a significantly lower median peak peripheral blood CD34+ cell count (68/µL vs. 36/µL, P = 0.048), and lower CD34+ cell yield on day 1 of collection (6.9 × 10⁶/kg vs. 2.4 × 10⁶/kg, P = 0.001). Six patients (8.1%) in the LD‐CY group experienced mobilization failure, compared to none in the plerixafor group. The total CD34+ cell yield was significantly higher in the plerixafor group (median 11.6 × 10⁶/kg vs. 7 × 10⁶/kg; P‐value = 0.001). Mobilization with LD‐CY was associated with increased (albeit statistically non‐significant) episodes of febrile neutropenia (5.4% vs. 0%; P = 0.24), higher use of intravenous antibiotics (6.7% vs. 3%; P = 0.45), and need for hospitalizations (9.4% vs. 3%; P = 0.24). The average total cost of mobilization in the plerixafor group was significantly higher compared to the LD‐CY group ($28,980 vs. $19,626.5 P‐value < 0.0001). In conclusion, in MM plerixafor‐based mobilization has superior efficacy, but significantly higher mobilization costs compared to LD‐CY mobilization. Our data caution against the use of LD‐CY in MM patients for mobilization, especially after induction with lenalidomide‐containing regimens. J. Clin. Apheresis 28:359–367, 2013. © 2013 Wiley Periodicals, Inc.     

Pegfilgrastim‐ versus filgrastim‐based autologous hematopoietic stem cell mobilization in the setting of preemptive use of plerixafor: efficacy and cost analysis

BACKGROUND: Plerixafor enhances the ability of filgrastim (FIL) to mobilize CD34+ cells but adds cost to the mobilization. We hypothesized that replacing weight‐based FIL with flat‐dose pegfilgrastim (PEG) in a validated cost‐based mobilization algorithm for patient‐adapted use of plerixafor would add convenience without increased cost. STUDY DESIGN AND METHODS: A single‐center retrospective analysis compared two consecutive cohorts undergoing FIL or PEG mobilization before autologous hematopoietic stem cell transplantation for multiple myeloma or lymphoma. FIL dose was 10 µg/kg/day continuing until completion of collection and a 12‐mg flat dose of PEG. Peripheral blood CD34+ cells (PB‐CD34+) enumeration was performed on the fourth day after initiation of growth factor. Subjects surpassing a certain target‐specific threshold of PB‐CD34+ started apheresis immediately while subjects with lower PB‐CD34+ received plerixafor with apheresis starting on the fifth day. RESULTS: Overall 68 of 74 in the FIL group and 52 of 57 patients in the PEG group met the mobilization target. Only one patient in each cohort required remobilization. Median PB‐CD34+ on Day 4 was significantly higher in patients in the PEG group (18.1 × 10⁶ vs. 28.7 × 10⁶ cells/L, p = 0.01). Consequently, patients in the PEG group were less likely to require administration of plerixafor (67.5% vs. 45.6%, p = 0.01). Cohorts had near identical mean number of apheresis sessions and comparable CD34+ yield. The estimated cost associated with growth factor was higher in patients in the PEG group, but it was counterbalanced by lower cost associated with use of plerixafor. CONCLUSION: Single administration of 12 mg of PEG is associated with better CD34+ mobilization than FIL allowing for effective, convenient mobilization with less frequent use of plerixafor.     

Effectiveness and cost analysis of "just-in-time" salvage plerixafor administration in autologous transplant patients with poor stem cell mobilization kinetics

BACKGROUND: Plerixafor is a recently Food and Drug Administration (FDA)‐approved CXCR4 antagonist, which is combined with granulocyte–colony‐stimulating factor (G‐CSF) to facilitate stem cell mobilization of lymphoma and myeloma patients. STUDY DESIGN AND METHODS: To evaluate the effectiveness and the related costs of a “just‐in‐time” strategy of plerixafor administration, we performed a retrospective cohort study comparing 148 consecutive lymphoma and myeloma patients in whom mobilization was attempted during 2008 before the Food and Drug Administration (FDA) approval of plerixafor with 188 consecutive patients mobilized during 2009 after FDA approval. RESULTS: Plerixafor was administered to 64 of 188 patients considered to be at risk for mobilization failure due to either their medical history (“high risk,” n = 23) or the occurrence of peripheral blood CD34+ count of fewer than 15 × 10⁶ cells/L with a white blood cell count of greater than 10 × 10⁹ cells/L after at least 5 days of G‐CSF administration (just‐in‐time, n = 41). The success rates of collecting a minimum transplant CD34+ cell dose (≥2 × 10⁶ cells/kg) or target cell dose (≥5 × 10⁶ lymphoma or ≥10 × 10⁶ CD34+ cells/kg myeloma) in the just‐in‐time patients compared favorably with the 36 poor mobilizers collected with G‐CSF alone: 93% versus 72% and 42% versus 22%, respectively. CONCLUSIONS: The use of plerixafor in selected high‐risk patients and poor mobilizers did not increase the total charges associated with stem cell collection when compared with poor mobilizers treated with G‐CSF alone. The targeted use of plerixafor increased the overall success rate of mobilizing a minimum number of CD34+ cells from 93% to 98% in patients with hematologic malignancies scheduled for autotransplant and increased the overall charges associated with stem cell collection in all patients by an average of 17%.     

Two‐year follow‐up after advanced core decompression

The so‐called “Advanced Core Decompression” (ACD) is a new option that tries to remove the necrotic tissue in patients with osteonecrosis of the femoral head (AVN) in a minimally invasive way by the use of a percutaneous expandable reamer and refilling with a resorbable and osteoinductive bone‐graft substitute. Seventy‐two hips of sixty patients with a mean follow‐up of 29.14 months after ACD have been included in this study. Patients underwent physical examination preoperatively and six weeks after surgery as well as at two further follow‐ups. Certain phases in disease progression and size of the necrotic lesion were differentiated on the basis of the classification of osteonecrosis of the femoral head by Steinberg.The femoral heads had collapsed in 24 cases (33%). Analysis of the survival rates with regard to defect size revealed that the largest defects had a significantly higher rate of femoral head collapse than the smaller defects. Clinical scores were also depending on defect size but also on disease stage. The current ACD technique has not yet achieved any significant improvement in the success rate of core decompression procedures. It can be concluded that the success of ACD depends especially on the defect size. Copyright © 2015 John Wiley & Sons, Ltd.     

Early versus late‐applied constraint‐induced movement therapy: A multisite,randomized controlled trial with a 12‐month follow‐up

Background and Purpose

A direct comparison between the effects of constraint‐induced movement therapy (CIMT) applied early after stroke and that of CIMT applied in the chronic phase has not been conducted. This study aimed to compare the long‐term effects of CIMT applied 6 months after stroke with the results of CIMT applied within 28 days post‐stroke.

Methods

This study was a single‐blinded, multicentre, randomized controlled trial with a crossover design. Forty‐seven patients received CIMT either early (within 28 days) or 6 months after stroke. Both groups received standard rehabilitation and were tested at 5 time points. The primary outcome measure was Wolf Motor Function Test (WMFT); the secondary measures were Nine‐Hole Peg Test (NHPT), the Fugl‐Meyer Assessment (FMA) of the upper extremity, Stroke Impact Scale, and Modified Rankin Scale (MRS).

Results

Compared with baseline data, both groups showed significant improvements in the primary and secondary outcome measures after 12 months. No significant differences between the 2 treatment groups were found before and after the delayed intervention group received CIMT at 6 months and during the 12‐month follow‐up. Both groups recovered considerably and showed only minor impairment (median FMA score of 64) after 6 months. The early intervention group showed an initially faster recovery curve of WMFT, NHPT, and MRS scores.

Discussion

In contrast to most CIMT studies, our study could not find an effect of CIMT applied 6 months after stroke. Our results indicate that commencing CIMT early is as good as delayed intervention in the long term, specifically in this group of patients who might have reached a ceiling effect during the first 6 months after stroke. Nevertheless, the early CIMT intervention group showed a faster recovery curve than the delayed intervention group, which can be a clinically important finding for patients in the acute phase.     

A retrospective study of autologous stem cell mobilization to guide an immediate salvage protocol using plerixafor for patients who mobilize stem cells poorly

The addition of plerixafor to G‐CSF decreases the risk of failed stem cell collection, but at considerable extra cost. Using a logistic regression model based on 354 autologous mobilizations, we have identified a local minimum peripheral blood CD34 count at which the probability of a successful collection is 50%. This seems an appropriate CD34 count at which to add immediate salvage plerixafor. J. Clin. Apheresis 28:378–380, 2013. © 2013 Wiley Periodicals, Inc.     

Storage of interim platelet units for 18 to 24 hours before pooling: in vitro study

BACKGROUND: The Atreus 3C system (CaridianBCT) automatically produces three components from whole blood (WB), a red blood cell (RBC) unit, a plasma unit, and an interim platelet (PLT) unit (IPU) that can be pooled with other IPUs to form a PLT dose for transfusion. The Atreus 3C system also includes a PLT yield indicator (PYI), which is an advanced algorithm that provides an index that is shown to correlate well with the amount of PLTs that finally end up in the IPU bag. The aim of our in vitro study was to compare the effects of holding WB overnight versus processing WB fresh (2‐8 hr), both with 18‐ to 24‐hour storage of the IPUs before pooling into a transfusable PLT dose. STUDY DESIGN AND METHODS: WB was processed either fresh (within 8 hr after collection, Atreus F) or after overnight storage (14‐24 hr, Atreus S) without agitation at 22 ± 2°C. After a subsequent resting time of 18 to 24 hours on a flat‐bed shaker, five IPUs were selected for pooling with 200 mL of PAS II for in vitro quality assessments during a 7‐day storage period (n = 10 in each arm). IPUs were selected for pooling using the PYI of the Atreus 3C system. RESULTS: During storage, the glucose concentration was lower (p < 0.05) and the lactate concentration was higher (p < 0.05) in Atreus S pools, but no differences in the glucose consumption rate were noted. Adenosine triphosphate levels and hypotonic shock response reactivity were higher in Atreus S (p < 0.05). No significant differences in PLT counts, contents, mean PLT volume, lactate dehydrogenase, pO₂, pCO₂, extent of shape change, and CD62P between groups were detected. pH was maintained higher than 6.8 (Day 7). With exception of 2 units in the Atreus S arm, swirling remained at greater than 2 in all units at all times. CONCLUSION: Our results suggest that PLTs prepared from fresh or overnight‐stored WB and pooled after 18 to 24 hours meet necessary in vitro criteria without any relevant differences between both groups. Using the PYI, comparable yields can be obtained between WB processed within 2 to 8 hours and WB stored overnight.