Hypercvad Induction Chemotherapy Is Associated with Higher Rates of Stem Cell Mobilization Failure in Mantle Cell Lymphoma ( MCL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3849-3849 ◽  
Author(s):  
Amandeep Salhotra ◽  
Shan Yuan ◽  
Joycelynne Palmer ◽  
Ibrahim Aldoss ◽  
Ni-Chun Tsai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Induction Chemotherapy ◽  
Bone Marrow Involvement ◽  
Median Number ◽  
The Other ◽  
High Dose ◽  
Newly Diagnosed ◽  
Cd34 Cells ◽  
Pbsc Mobilization

Abstract Background: MCL patients deemed fit for high dose regimens undergo induction therapy with rituximab and chemotherapy (HyperCVAD/CHOP/bendamustine) followed by consolidation with ASCT (autologous stem cell transplantation). R-HyperCVAD is a dose intense regimen with high response rates for MCL when used in the upfront setting (ORR 97%; CR 38%; Romaquera JE, JCO 2005). R-bendamustine and R-CHOP are contemporary regimens with similar efficacy (ORR 85-93%; Rummel MJ, Lancet 2013). In a recent randomized phase II trial (SWOG 1106) accrual to the HyperCVAD arm was stopped due to higher than expected rates of peripheral blood stem cell (PBSC) mobilization failure. Methods: To assess the impact of these regimens on PBSC collection, we performed a retrospective analysis of newly diagnosed MCL patients undergoing induction chemotherapy with R-HyperCVAD versus R-CHOP/R-bendamustine and referred to transfusion medicine for PBSC collection prior to ASCT from 01/2009 to 12/2013. Patients were not allowed any salvage chemotherapy. The primary end point was successful stem cell collection defined as ability to collect ≥2.1 million CD34 cells/Kg. Secondary endpoints were number of days of apheresis, use of pleraxifor as mobilization salvage and total number of CD34+ cells collected. Results: A total of 91 MCL patients were eligible for analysis (Table 1). Patients who received HyperCVAD were younger at the time of collection (median: 56 vs 62 years; p <0.01) and were referred for collection earlier (median time from diagnosis to collection start: 4.5 vs. 6.4 months; p<0.01). There were no other baseline differences between the two groups in terms of gender, bone marrow involvement, stage of disease at presentation and use of plerixafor. While the median number of apheresis days were comparable: 4 (range: 1-9) for the HyperCVAD group and 3 (range: 2-8) for the other group (p=0.21), 18% patients in the Hyper-CVAD group failed to collect adequate numbers of PBSC (defined as < 2.1 ×10 6/Kg) compared to 4% in the other group (p=0.05). Additionally, the median number of CD34+ cells collected was lower in HyperCVAD group (p=0.05). After adjusting for baseline differences in age and timing of collection, for a patient who received HyperCVAD, the odds of failing to collect were 7.28 times higher (95% CI: 1.01, 52.57) than the odds for a patient who received a non-HyperCVAD induction regimen (p=0.05). Ultimately, 81/91 (89%) patients proceeded to high dose chemotherapy and ASCT [82% in HyperCVAD versus 96% in non-HyperCVAD (p=0.06)]. Four of the remaining 10 patients with mobilization failure (all from HyperCVAD arm) proceeded to Allogeneic HCT, the remaining 6 patients did not receive any further treatment. Conclusion: Patients with MCL receiving R-HyperCVAD chemotherapy in the frontline setting have a significantly higher rate of PBSC mobilization failure and collect significantly fewer CD34+ PBSCs when compared to patients treated with comparable regimens. R-HyperCVAD should be used with caution in patients with newly diagnosed MCL who are eligible for ASCT. Some patients failing mobilization may be salvaged with use of plerixafor. Table 1: Patient, Transplant Characteristics Variable Hyper-CVAD, n=45Median (Range)N (%) Other, n=46Median (Range)N (%) Patient Gender Female Male 9 (20) 36 (80) 12 (26) 34 (74) Age at Collection Completion (years) 56 (40 – 68) 62 (36 – 74) Time from Diagnosis to Start of Collection (months) 4.5 (2.3 – 65.3) 6.4 (3.9 – 69.4) Stage at Diagnosis I II III IV 1 (2) 3 (7) 2 (4) 39 (87) 2 (4) 1 (2) 6 (13) 37 (81) Bone Marrow Involvement at Diagnosis No Yes Not Done 9 (20) 35 (78) 1 (2) 13 (28) 32 (70) 1 (2) Treatment after Chemotherapy Auto Transplant Allo Transplant No Transplant 37 (82) 4 (9) 4 (9) 44 (96) 0 (0) 2 (4) Mozobil Era (08/16/2009) Pre Post 8 (18) 37 (82) 3 (7) 43 (93) Mozobil Usage No Yes 29 (64) 16 (36) 30 (65) 16 (35) Number of Collections 4 (1 – 9) 3 (2 – 8) Total CD34 4.5 (0.3 – 100.5) 5.3 (0.7 – 76.6) Total CD34 (Failure Rate) < 2.1 >/= 2.1 8 (18) 37 (82) 2 (4) 44 (96) Disclosures Chen: Seattle Genetics: Honoraria, Research Funding, Speakers Bureau.

Clinical and Prognostic Relevance of Magnetic Resonance Imaging of the Spine in Newly Diagnosed Multiple Myeloma Patients Receiving Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4885-4885
Author(s):  
Patrizia Tosi ◽  
Alessandro Petrucci ◽  
Lucia Pantani ◽  
Elena Zamagni ◽  
Paola Tacchetti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
High Dose ◽  
Newly Diagnosed ◽  
Resonance Imaging ◽  
Focal Lesions ◽  
Free Survival ◽  
Focal Pattern

Abstract Abstract 4885 Magnetic resonance imaging (MRI) of the spine has demonstrated to be a useful tool for a correct staging of multiple myeloma (MM), as it is more sensitive than plain x-rays in detecting vertebral lesions. Furthermore, both pattern of bone marrow involvement (focal, diffuse or normal), and number of focal lesions can be detected, and this could contribute to better define the prognosis and the outcome of newly diagnosed patients. In the present study we prospectively evaluated the clinical and prognostic role of spinal MRI in 152 newly diagnosed MM patients (89M, 63F, median age = 56yrs) that subsequently received high-dose chemotherapy and autologous stem cell transplantion, either single (n=43) or double (n=109). Pattern of marrow involvement was normal in 11% of the cases, diffuse in 20% and focal in 69%, with 34% of the patients showing > 7 focal lesions. Patients with a diffuse pattern or a focal pattern with > 7 lesions showed a significantly higher bone marrow plasma cell infiltration (p=0.04) and beta2 microglobulin values (p= 0.04) as compared to patients with a focal pattern with < 7 lesions. Response rate to the assigned treatment program was similar in the three groups of patients, with > VGPR obtained in 63% of the patients with a diffuse pattern, and in 70% of those with a focal pattern. Median progression-free survival (PFS) was significantly longer in patients with < 7 focal lesions as compared to those with >7 lesions or a diffuse pattern (55 vs 46 months p=0.05). Normalization of MRI was more frequently obtained in patients with < 7 lesions (67% vs 38% in patients with > 7 lesions, p=0.005); patients achieving a normal MRI pattern showed a significantly longer PFS (67 months) as compared to patients failing to achieve a negative MRI at the end of treatment (p=0.0000). According to our data, MRI confirms its prognostic role in newly diagnosed MM receiving high-dose therapy and autologous stem-cell transplantation; a diffuse pattern of bone marrow involvement or a focal pattern with > 7 lesions are predictive of a more aggressive outcome of the disease; furthermore normalization of MRI pattern after therapy is predictive of a longer progression-free survival Disclosures No relevant conflicts of interest to declare.

Outcomes of Patients (pts) with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Treated with Hyper-CVAD-Based Chemotherapy Regimens: MD Anderson Case Series

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4263-4263
Author(s):  
Naveen Pemmaraju ◽  
Deborah A. Thomas ◽  
Hagop M. Kantarjian ◽  
Sherry Pierce ◽  
Susan O’Brien ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematologic Malignancy ◽  
Bone Marrow Involvement ◽  
Median Number ◽  
High Dose ◽  
Cell Transplant ◽  
Multi Agent ◽  
Md Anderson

Abstract Abstract 4263 Background: BPDCN, formerly known as CD4 + CD56 + hematodermic tumor or blastic NK cell lymphoma, is an exceedingly rare and aggressive hematologic malignancy. Although most pts with BPDCN receive intensive multi-agent chemotherapy and are referred for consideration of SCT, their prognosis remains poor and little is known about how to effectively treat these pts. Objective: We therefore reviewed the characteristics and outcome of all pts with BPDCN who were referred to us and treated with various Hyper-CVAD-based regimens to identify patterns of disease and response that might be useful for future pts. Methods: We conducted a retrospective chart review of pts meeting the following criteria: pathological diagnosis of BPDCN confirmed by an experienced hematopathologist; age 18 or older; treated at MD Anderson Cancer Center, and at least one documented follow-up visit. Results: We identified a total of 5 pts who presented between October 2008 and July 2011. All were male. Median age was 65 yrs (range 20–86). At diagnosis, 4 of the 5 pts had bone marrow involvement; 2 pts had skin involvement, and 1 pt with inguinal lymph node involvement. Immunophenotype by flow cytometry was CD4+(4/5 pts) CD56+(1/5 pt negative), TCL-1+ (4/5 pts, unknown in 1 pt) and partial loss/negative for CD3 and CD8 (5/5 pts). Cytogenetics were complex in 2 pts and diploid in 3. Baseline median WBC was 5.4 (2.2–76.5) and baseline median platelet count was 99 (48–112). Median baseline bone marrow blasts: 21% among 4/5 pts (one not evaluable). No pts had prior history of hematologic malignancy. One pt had a daughter with CLL. All 5 pts received first-line therapy with Hyper-CVAD (1 pt received chemotherapy with cyclophosphamide, adriamycin, vincristine, prednionse (CHOP) x1 cycle and then went on to get Hyper-CVAD × 4 cycles afterwards once diagnosis was confirmed as BPDCN). Hyper-CVAD consists of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and Dexamethasone, alternating with high-dose methotrexate and cytarabine for a total of 8 cycles followed by a 24 to 32 months lasting POMP (prednisone, vincristine, methotrexate, mercaptopurine) maintenance. All pts were referred to stem cell transplantation (SCT) if they had a donor and there were no other contraindications for SCT. All pts received a median number of 4 cycles (range 1–5) of Hyper-CVAD and median number of total lines of chemotherapy regimens was 3 (range 1–4). Three pts went on to receive a stem cell transplant (SCT), (2= allogeneic (allo) SCT, 1= autologous (auto) SCT), their outcomes showed: 1 pt achieved CR2 but died of relapsed disease status post auto SCT, 1 pt alive in CR2 for 2 months status post 1 antigen-mismatched allo SCT, 1 pt alive with bone marrow CR1 for 4 months status post allo SCT. For the other 2 pts not receiving SCT, their outcomes were: 1 pt died during first induction course, 1 pt achieved CR1 for 4 months then relapsed and died. The median duration of CR1 was 4 months (4–18). Only one pt received radiation treatment because of a residual mediastinal mass after 3 cycles of Hyper-CVAD despite bone marrow remission. Three of the 5 patients have died with a median overall survival of 32 months (pt with longest follow-up was the 1 pt with no bone marrow involvement at diagnosis and died at 32 months). Conclusion: BPDCN is a rare but aggressive malignancy with dismal prognosis in most pts. Despite intensive multi-agent chemotherapy and SCT, response rates are low and survival is short. A better understanding of the biologic basis of the disease and novel treatment approaches are crucial for improving outcome. Disclosures: No relevant conflicts of interest to declare.

Hypogammaglobulinemia Following Rituximab and High-Dose Therapy and Autologous Stem-Cell Transplant: Incidence and Predictors of Prolonged Immunoglobulin Deficiencies

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4351-4351
Author(s):  
Nancy Pennell ◽  
Matthew Cheung ◽  
Lisa K Hicks ◽  
Rena Buckstein ◽  
Kevin R Imrie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Marrow Involvement ◽  
Median Number ◽  
Study Entry ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Transformed Lymphoma ◽  
Aggressive Histology

Abstract High-dose therapy and autologous stem cell transplantation (HDT/ASCT) and rituximab immunotherapy have been increasingly applied in the management of non-Hodgkin’s lymphomas (NHL). Although both approaches have been individually associated with B-cell depletion and hypogammaglobulinemia, the incidence, time course, and predictors of prolonged deficiencies following a combined treatment approach is unknown. Methods: We completed a series of prospective phase II studies of HDT/ASCT combined with rituximab for patients with relapsed follicular lymphoma (FL) or diffuse large B cell lymphoma (DLBCL). In two phase II trials of patients with FL (R/Tx and R-IFN/Tx), patients received 9 infusions of rituximab 375mg/m2 as both an in vivo purge and as maintenance post HDT/ASCT. In a trial with relapsed DLBCL or transformed lymphoma, patients received 8 infusions with rituximab 375mg/m2 only as part of the salvage chemotherapy regimen (R-ESHAP/Tx). Immunoglobulin levels were expressed as percentages with 100% representing the lower limit of normal at the institutional lab. Hypogammaglobulinemia was defined as &lt;75% of this lower limit. A time-to-recovery from hypogammaglobulinemia was determined by Kaplan-Meier statistics. Results: Fifty-one patients with FL were transplanted and were subsequently treated with maintenance rituximab (R/Tx study) or with maintenance rituximab (MR) and interferon-alpha (R-IFN/Tx). Twenty-six patients with relapsed aggressive-histology lymphoma were transplanted with the R-ESHAP salvage regimen. The mean age of the FL patients was 45 and the mean age of the aggressive-histology lymphoma patients was 49. The median number of prior therapies was 1 (range 1–3) for the FL patients and bone marrow involvement at study entry was present in 63%. The median number of prior therapies was 1 (range 1–5) for the aggressive-histology lymphoma patients and bone marrow involvement was present in 15%. Baseline IgG hypogammaglobulinemia was seen in 18% of patients with relapsed FL and 15% of patients with relapsed DLBCL/transformed lymphoma. Median baseline Ig levels in each study are displayed in Figure 1. Patients with FL undergoing HDT/ASCT and MR (combined R/Tx and R-IFN/Tx studies) had prolonged IgG hypogammaglobulinemia compared to patients with aggressive-histology lymphoma (log-rank p=0.0047; see Figure 2). The median time-to-recovery from hypogammaglobulinemia had not been reached after a median follow-up of 42 months. Similarly, IgM level recovery was delayed in the FL group compared to the aggressive-histology patients (p=.0001), although late recovery was noted for this Ig subtype (median time-to-recovery 36 months post-ASCT). Univariate analyses revealed that persistent hypogammaglobulinemia (at 24 months) was associated with FL histology (vs. DLBCL/transformed; p=0.006), bone marrow involvement at study entry (p=0.008), and hypogammaglobulinemia at study entry (p=0.026). Factors not associated with persistent hypogammaglobulinemia included: number of prior therapies, age, and administration of maintenance interferon-alpha. Post-transplant (&gt;3 months) infections included herpes zoster reactivation (n=7) and pneumonia (n=8). One individual in the R-ESHAP/Tx study died of PCP pneumonia 4 months post HDT/ASCT. A relationship between grade III-IV infections and prolonged hypogammaglobulinemia was not evident on univariate analysis (data not shown). Conclusions: Patients with follicular lymphoma undergoing high dose therapy and stem cell transplantation together with rituximab maintenance are likely to experience a prolonged hypogammaglobulinemia whereas this is less likely with patients with aggressive-histology lymphoma undergoing similar doses of rituximab as part of their salvage therapy. Further research is required to elucidate the relative contributions of disease histology, bone marrow involvement, baseline hypogammaglobulinemia, timing of rituximab infusions or other factors not yet identified. Figure Figure Figure Figure

Pegfilgrastim Versus Filgrastim To Accelerate Hematopoietic Recovery after High Dose Melphalan and Autologous Hematopoietic Stem Cell Transplant (ASCT) for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5193-5193
Author(s):  
Rebecca L. Olin ◽  
Selina M. Luger ◽  
David L. Porter ◽  
Stephen J. Schuster ◽  
Donald Tsai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cohort Study ◽  
Stem Cell ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Median Number ◽  
High Dose ◽  
Hematopoietic Recovery ◽  
Cd34 Cells ◽  
High Dose Melphalan

Abstract High-dose melphalan followed by ASCT is a common component of the early treatment for patients with multiple myeloma. Daily subcutaneous injections of filgrastim (Neupogen) at 5 ug/kg/day until ANC &gt; 500/ul are routinely administered at our center from day +4 following ASCT, in order to accelerate hematopoietic recovery and lessen neutropenic complications. Pegfilgrastim (Neulasta) as a single 6 mg fixed dose subcutaneous injection has been shown to have similar efficacy and ease of use when compared to filgrastim in the non-transplant setting, but little data is available in the transplant setting. We began using pegfilgrastim day +1 following ASCT for patients with multiple myeloma and performed a retrospective cohort study comparing those who received filgrastim (n=6) with those who received pegfilgrastim (n=11). Transplants occurred between July 2002 and January 2004 and included all patients transplanted for myeloma in that time period for whom sufficient data was available. All patients had at least 2 x 106 CD34+ cells/kg peripheral stem cells harvested after cytoxan and filgrastim mobilization. Main outcome measures were: days from stem cell infusion to WBC nadir, days to ANC&gt;500/ul, and days to ANC&gt;1000/ul. Subjects were excluded if CBCs were drawn less frequently than every four days. There were no significant differences between the filgrastim and pegfilgrastim groups with respect to the following demographic variables: age, gender, hemoglobin, creatinine, calcium, albumin and beta-2 microglobulin at diagnosis. The groups were also balanced with respect to SPEP, UPEP, presence of lytic lesions and number of prior lines of therapy. The median number of CD34+ cells infused was similar: 5.7 x 106 in the filgrastim group vs 4.8 x 106 in the pegfilgrastim group (p=0.28). After transplant, median number of days to WBC nadir in the filgrastim group (FG) was 7 (range 5–9) vs 6 (range 5–8) in the pegfilgrastim group (PG) (p=0.31). However, median number of days to ANC&gt;500/ul in the FG was 11.5 (range 11–17) vs 10 (range 9–12) for PG (p=0.02). Similarly, median number of days to ANC&gt;1000/ul was 12 (range 11–17) for FG vs 11 (range 10–13) for PG (p=0.03). Five of six patients in the FG had neutropenic fever after transplant, compared to five of eleven patients in the PG (p=0.30). Currently, no significant differences in infection or relapse rates between groups have been noted and there were no deaths in either group. In this retrospective cohort study, pegfilgrastim was safe and at least equivalent to filgrastim for accelerating hematopoiesis after ASCT for multiple myeloma. Furthermore, there was no significant difference in the incidence of neutropenic fever, infection and survival, suggesting a similar clinical utility.

Influence of Stem Cell Mobilization After Cyclophosphamide, Thalidomide and Dexamethasone (CTD) Regimen in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1927-1927
Author(s):  
Jae-Sook Ahn ◽  
Deok-Hwan Yang ◽  
Sung-Hoon Jung ◽  
Soo-Young Bae ◽  
Yeo-Kyeoung Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Induction Therapy ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Median Number ◽  
High Response Rate ◽  
Cell Yield ◽  
Newly Diagnosed ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 1927 Backgrounds: CTD regimen has been known as an effective induction therapy in patients with newly diagnosed MM. But, there were inconsistent results for the autologous stem cell yield for transplantation. The aim of present study was to identify the influence of CTD therapy on outcome of peripheral blood stem cell (PBSC) collection. Methods: Forty-eight patients received 4 cycles of CTD therapy. Stem cells were mobilized with cyclophosphamide (3.0 g/m2) and G-CSF (10 ƒÝg/kg, daily) or G-CSF alone. Patients failing to collect ≤ 4.0 × 106 CD34+ cells /kg received a second mobilization courses. Results: The median age at diagnosis was 56 years (range, 39–69). Median duration from start of CTD therapy to first collection was 4.6 months (range, 3.3–8.7). Forty-four patients were mobilized with cyclophosphamide following with G-CSF and 4 patients with G-CSF alone. The median day of apheresis was 3 days (range, 2–7). The response rate for CTD regimen at mobilization was 10% (5/48) of CR, 25% (12/48) of VGPR and 63% (30/48) of PR. A median number of harvested CD34+ cells was 8.6 × 106 cells/kg. At the first mobilization, 83% (40/48) of patients had been reached the minimal PBSC collection target of ≥ 2.0 × 106 CD34+ cells/kg and 71% (34/48) of patients achieved the collection ≥ 4.0 × 106 CD34+ cells/kg. At the end of second mobilization, 90%(43/48) of patients had yields of at least ≥ 2.0 × 106 CD34+ cells/kg and 77% (37/48) of patients had yields of ≥ 4.0 × 106 CD34+ cells/kg. During mobilization period, three patients were developed grade 3/4 non-hematologic adverse events. Conclusion: CTD regimen is an effective induction therapy in patients with newly diagnosed MM showing high response rate and acceptable rate of autologuos stem cell yield without any detrimental effect for the following stem cell collection. Disclosures: No relevant conflicts of interest to declare.

Sequential High-Dose Dexamethasone and Response Adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) Induction Chemotherapy Followed by High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma; Open-Labelled, Multicenter Phase 2 Study (KMM-94 Study)-Interim Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2044-2044
Author(s):  
Jin Seok Kim ◽  
Cheolwon Suh ◽  
June-Won Cheong ◽  
Kihyun Kim ◽  
Yang Soo Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Induction Chemotherapy ◽  
Induction Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Younger Patients ◽  
High Dose Dexamethasone

Abstract Abstract 2044 Background: Induction treatment followed by autologous stem cell transplantation (ASCT) is the standard therapy for the newly diagnosed younger patients with multiple myeloma (MM). Although new drugs such as lenalidomide or bortezomib have been shown the promising results as induction treatment, many different type of induction treatment regimens still have been used. We evaluate the efficacy and safety of the short course of high dose dexamethasone (HD dexa) and the response adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy in the newly diagnosed younger patients with MM. Methods: 107 newly diagnosed patients with MM from 21 institutions received 2nd cycles of HD dexa followed by PAD or VAD chemotherapy according to the response to the initial high dose dexamethasone. The primary endpoint was complete response (CR) + near CR rate after ASCT. Among 107 patents enrolled this study from November 2009, 25 patients (23%) have been dropped out. This trial will be continued until total 210 patients will be enrolled. The trial is registered on National Cancer Institute website, number NCT01255514. Results: One hundred seven patients (58 male, 49 female) were enrolled (median age; 56). 26 (24%) light chain disease were included. 31 (29%) patients were D-S stage II and 67 (63%) were stage III. According to the ISS, 23 (22%) patients had stage I, 51 (48%) had stage II and 33 (31%) had stage III. 26 (24%) patients had abnormal cytogenetics. There were 31% del13, 7% del17, 19% t(4;14), 15% t(14;16) and 28% t(11;14) in FISH analysis. Among the 82 evaluable patients, CR + PR rate was 48% (39/82) after 2nd cycles of HD dexa therapy. 39 patients (48%) received subsequent VAD chemotherapy and 43 patients (52%) received PAD chemotherapy. Among the 64 patients finished VAD or PAD chemotherapy, CR + PR rate was 83% (79%, 26/33 in VAD group vs. 87%, 27/31 in PAD group). 56 patients were finished ASCT until now. CR + near CR rate after ASCT were 61% (58% in VAD group vs 63% in PAD group). Mortality rate of this trial was 13% (11/82). The cause of death was disease progression (n=3), bleeding (n=1) and infections (n=7). Among 82 patients in whom VAD or PAD chemotherapy was actually performed, 1 year overall survival (OS) rate was 84.7%. 1 year survival rate was 93.8% versus 77.2% (P=0.049) with VAD versus PAD (median follow-up; 9.1 months). Conclusion: Risk adapted approach using initial steroid response showed good response results after ASCT compared with previous trial (CR + near CR rate of IFM 2005-01trial-Bortezomib+dexa induction & ASCT was 35%, J Clin Oncol. 2010;28:4621–9) The MM patients who had poor response to HD dexa also showed similar good response rate after ASCT compared with the patients who had good response to HD dexa treatment in this trial. PAD re-induction therapy after failure of initial steroid induction treatment might overcome the inferior results in the high risk MM patients. Therefore, initial steroid response adapted strategy might be the more cost-effective approach in the newly diagnosed ASCT eligible MM patients. Disclosures: No relevant conflicts of interest to declare.

Plerixafor and G-CSF For Autologous Stem Cell Mobilization In AL Amyloidosis: A Single Center Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4516-4516
Author(s):  
Esha Kaul ◽  
Gunjan L Shah ◽  
Chakra P Chaulagain ◽  
Raymond L. Comenzo
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Initial Therapy ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Cell Mobilization

Background Risk-adapted melphalan and stem cell transplant (SCT) is standard initial therapy for a minority of patients with systemic AL amyloidosis (Blood 2013;121: 5124; Blood 2011;118: 4298). Stem cell mobilization is often accomplished with high dose G-CSF (16μg/kg/d) (Blood 2011;118:4346). In the current era with effective new agents such as bortezomib, many AL patients are receiving initial therapy and achieving profound rapid cytoreduction with organ improvement (Blood 2012;119:4391; Blood 2011;118:86). But not all patients respond and in some cases the duration of response is limited. In addition, the use of SCT for consolidation after an initial response, although reasonable, has not been systematically evaluated. Whether SCT is employed as consolidation or as a second- or third-line option, the efficacy and tolerance of mobilization become important issues. Because AL patients have organ involvement limiting chemotherapy-based mobilization options, we decided to explore the option of Plerixafor and G-CSF for stem cell mobilization, based on the phase III experience in MM (Blood 2009;113:5720). We now report the first experience with this mobilization approach in AL. Patients and Methods Patients were evaluated and diagnosed by standard criteria including, in all cases, tissue biopsies showing amyloidosis. They were mobilized and collected between 4/16/12 and 6/19/13 with G-CSF 10μg/kg/d subcutaneously (SC) for 5 days (continued through collection process) and Plerixafor adjusted for renal function starting on day 4 and continuing until collection was completed. Results We report on 10 patients whose median age at mobilization was 58 years (range 46-72), 60% of whom were men. Median number of organs involved was 2 (range 1-3). Heart and kidneys were the most frequently involved organs (7 patients in each group). Median time from diagnosis to mobilization was 9 months (range 2-123). Eight patients had received prior bortezomib-based therapy. The median number of cycles was 3 (range 0-6). One had received a prior MEL 140 transplant 10 years prior and had relapsed, and 2 were treatment naïve, one of whom was 1 year status post orthotopic heart transplant. At the time of mobilization, 3 patients had non-responsive hematologic disease, 3 had achieved PR, 1 VGPR and 1 had achieved CR. Five patients had a creatinine ≥ 1.5 mg/dL including 2 patients on hemodialysis. The target cell dose was 10x106CD34/kg for all but one patient (with previous history of transplantation). The median number of collections was 2 (range 2-3). On day one, the median number of CD34+ cells collected per kg was 3.6 x106 (0.4-6x106) and on day two 6.4 x106 (2.7-19x106). The median total CD34+ cells collected per kg was 12.5x106 (5-18x106). Two patients had grade 1 bleeding from the catheter site during apheresis and one patient had dyspnea with suspected fluid overload which responded to a single dose of intravenous furosemide. There were no significant toxicities observed with Plerixafor in mobilization. All patients went on to receive high dose chemotherapy with melphalan followed by autologous stem cell transplant. The median length of hospital stay was 25 days (18-32). The median stem cell dose infused was 7.6x106CD34/kg and median days to ANC > 500 was 11 (10-22), to platelets > 20K untransfused 22 (15-44) and to lymphocytes > 500/μl 14.5 (11-25). One patient who had VOD and persistent thrombocytopenia was given the remainder of his stem cells on day +31 with full recovery and normalization of the blood counts by day +65. Conclusions In the era of more effective initial therapies, an era in which AL patients are living longer, many with moderate organ damage, mobilization with Plerixafor and G-CSF was well tolerated and made it possible to collect ample numbers of CD34+ cells with limited leukaphereses in previously treated patients and in those with advanced renal failure. This approach not only allowed the collection of sufficient CD34+ cells for optimal immediate stem cell dosing but also permitted the cryopreservation of aliquots for post-SCT boost and potentially for future cell-based therapies. Disclosures: Comenzo: Millenium: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Prothena: Research Funding; Teva: Research Funding.

Tandem high-dose therapy with autologous stem cell support for small-cell lung cancer (SCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17033-17033
Author(s):  
J. N. Machatschek ◽  
G. Kobbe ◽  
R. Haas ◽  
U. P. Rohr
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Induction Chemotherapy ◽  
Cox Regression ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
Platelet Recovery ◽  
Dose Therapy

17033 Background: We evaluated the therapeutic efficacy of tandem high-dose chemotherapy followed by autologous peripheral stem-cell transplantation (PBSCT) in patients with newly diagnosed SCLC in complete remission or very good partial response after induction chemotherapy. Methods: Between 1996 and 2000, 19 patients with newly diagnosed SCLC in CR or very good PR after two cycles of induction chemotherapy (cisplatin 90 mg/m2 day 1, etoposide 120 mg/m2 day 1–3, ifosfamide 1500 mg/m2 day 1–4) received a tandem high-dose chemotherapy (cyclophosfamide 2000 mg/m2 day 1 and 2, etoposide 700 mg/m2 day 1–3, carboplatin 1200 mg/m2 day 1) followed by PBSCT. Following transplantation, patients received concurrent chest and cranial radiotherapy to a total dose of 45 Gy and 30 Gy, respectively. Results: Of 19 patients with SCLC, 18 had stage III and one stage IV disease. The median age was 50.7 years. Median time to leukocyte-recovery above 1000/μl and platelet-recovery above 20.000/μl was 12 days and 9 days, respectively. The median follow-up was 6.38 years (range 5.11–7.23) for surviving patients. There were no transplant-related deaths and toxicity was moderate. Using the Kaplan-Meier method, the 2- and 5-year survival rates after high-dose therapy were 42% and 32% respectively. Median time to relapse was 0.7 years (range 0.2–4.6). The mean survival was 36.8 months. This outcome compared favourably to a group of 77 patients who did not receive high-dose therapy but responded to conventional chemotherapy (mean survival 11.4 months). Using the Cox regression model, among all patients response to induction, normal LDH and PBSCT were associated with favourable outcome. Conclusions: Our findings suggest that patients with or near complete response after conventional therapy might benefit from tandem high-dose therapy with PBSCT with tolerable toxicicity. No significant financial relationships to disclose.

Comparative efficacy of reduced or standard doses of lenograstim for peripheral blood stem cell mobilization and transplantation: A randomized study in patients undergoing autologous peripheral stem cell transplantation

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7099-7099
Author(s):  
M. Ozturk ◽  
F. Arpaci ◽  
S. Ataergin ◽  
A. Ozet ◽  
T. Cetin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Dose Group ◽  
Low Dose ◽  
Peripheral Blood Stem Cell ◽  
Standard Dose ◽  
Randomized Study ◽  
Median Number ◽  
Cd34 Cells ◽  
Pbsc Mobilization

7099 Background: 10 microg/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. However,in our previous randomized study we demonstrated that a 7.5 microg/kg/day dose of lenograstim has been as efficacious as 10 microg/kg/day of filgrastim. In this study, we investigated whether a reduced dose of lenograstim is equavalent to standard dose for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. Methods: A total of 49 consecutive patients were randomized to either low dose (7.5 microg/kg/day, n = 24) or standard dose (10 microg/kg/day, n = 25) of lenograstim. These two groups were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each dose of lenograstim was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, lenograstim was given at 5 microg/kg/day until leukocyte engraftment. Results: Successful mobilization with the first apheresis, was achieved in 10/24 (42%) patients in low dose group versus 14/25 (56%) patients in standard dose group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G-CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Conclusions: Lenograstim 7.5 microg/kg/day is as efficious as Lenograstim 10 microg/kg/day for autologous PBSC mobilization and transplantation. No significant financial relationships to disclose.

Impact of Prior Lenalidomide Treatment on Peripheral Blood Stem Cell (PBSC) Mobilization in Untreated Multiple Myeloma (MM) Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3612-3612
Author(s):  
Amitabha Mazumder ◽  
Jonathan Kaufman ◽  
Sagar Lonial ◽  
Sundar Jagannath ◽  
David Vesole
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Induction Therapy ◽  
Gm Csf ◽  
Cd34 Cells ◽  
Bone Marrow Plasma ◽  
Marrow Stroma ◽  
Number Of Cycles ◽  
Pbsc Mobilization

Abstract Background: Immunomodulatory drugs (e.g. thalidomide and lenalidomide) are increasingly being used for induction therapy prior to stem cell harvest in MM. We have previously reported that induction therapy with a thalidomide-based regimen leads to a lower yield of stem cells when compared to bortezomib. This resulted in a reduced yield of stem cells per collection and an increased number of phereses required to reach our target goal. Delay in engraftment of platelets by a median of 1 day was also observed. We now report lower PBSC yields in patients receiving lenalidomide induction therapy. Methods: Data was pooled from 2 centers on patients who received lenalidomide induction therapy followed by PBSC mobilization. Twenty of 28 patients received G-CSF 10 micrograms/kg for four days; 8 patients were mobilized with 7.5 mcg/kg G-CSF plus 7.5 mcg/kg GM-CSF for 5 days. Results: Eight of 28 patients (40%) failed to collect sufficient cells for even 1 transplant (less than 2 x 106 CD34+ cells/kg. Of note, 2 of these patients also failed to mobilize sufficient stem cells when treated with the CxCR4 inhibitor AMD3100 plus G-CSF on a compassionate use protocol. These patients subsequently had successful mobilization following cyclophosphamide chemotherapy mobilization. Our data mirrored those of Kumar et al (Leukemia 2007 Jun 21; [Epub]) in several aspects. After lenalidomide therapy, there was a decrease in total number of CD34+ cells/kg in day 1 collections and total number of days required to collect sufficient CD34+ cells when compared to chemotherapy or bortezomib induction therapy. However, our data differed from those of Kumar et al regarding the correlation of number of cycles of lenalidomide therapy and subsequent PBSC collection. Kumar et al reported no failures in patients who had less than 6 cycles of lenalidomide. In contrast, 5 of our failures had received only 4 or 5 cycles of lenalidomide. Conclusions: Patients treated with lenalidomide induction therapy have lower stem cell yields with growth factor mobilization. Biologically, the action of Imids may be different from those of bortezomib on the bone marrow stroma. These lower yields may become clinically important when attempting to obtain stem cells from elderly patients, those with prior radiation therapy or with higher bone marrow plasma cell infiltration. Our group has elected to use cyclophosphamide for mobilization of patients treated with prior lenalidomide and we have been successful in 4/4 patients so far.

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