Long-Term Outcome Of Patients With AL Amyloidosis Treated With High-Dose Melphalan and Stem Cell Transplantation: 19 Year Experience At a Single Center

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3328-3328 ◽  
Author(s):  
Vaishali Sanchorawala ◽  
Gheorghe Doros ◽  
Karen Quillen ◽  
John Mark Sloan ◽  
Anthony C Shelton ◽  
...  
Keyword(s):  
Stem Cell ◽  
Group Performance ◽  
Performance Status ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Term Survival ◽  
Cell Mobilization

Abstract Aggressive treatment of AL amyloidosis with high dose intravenous melphalan followed by autologous stem cell transplant (HDM/SCT) is effective in inducing hematologic and clinical remissions associated with prolonged survival. We have performed 593 transplants from July 1994 to December 2012 in the Amyloidosis Center at Boston Medical Center/Boston University School of Medicine. Patients were enrolled in several sequential institutional review board–approved protocols during the 19-year study period. Eligibility criteria for all protocols required biopsy proof of amyloid disease; evidence of a plasma cell dyscrasia and exclusion of other types as appropriate; at least one major affected organ; and adequate measures of cardiac and pulmonary function, and performance status. Functional measures included cardiac ejection fraction 40% or greater, absence of symptomatic pleural effusions, absence of heart failure or arrhythmias resistant to medical management, oxygen saturation of 95% or greater on room air, lung diffusion capacity of 50% or more of predicted, supine systolic blood pressure of 90 mm Hg or greater, and Southwest Oncology Group performance status score of 2 or less unless limited by peripheral neuropathy. Age, renal function, time from diagnosis, prior therapy, and details of the conditioning regimen varied among the trials. Overall, the median age of patients treated with HDM/SCT was 57 years (range, 28-80). Treatment-related mortality (TRM) defined as death occurring within 100 days after SCT occurred in 51 patients, leading to overall TRM of 9% (n=51/593). Additionally, there were 11 deaths during stem cell mobilization and collection phase. No death has occurred since 2005 during stem cell mobilization and collection and TRM has improved to 5% (n=11/235). Total of 324 patients (55%) received full dose melphalan at 200 mg/m2 and 269 (45%) received modified dose melphalan at 100-140 mg/m2 per protocol, based upon age and organ function. Hematologic CR, as defined by international consensus criteria, occurred in 40% (n=202/508) of evaluable patients measured at 6-12 months post SCT; by intention-to-treat the CR rate was 34%. Hematologic CR occurred in 44% (n=129/291) patients who received 200 mg/m2 of HDM compared to 34% (n=73/217) patients who received 100-140 mg/m2 of HDM (chi square p=0.015). Hematologic relapse occurred in 40 patients (20%) with CR at a median of 3.9 years (range, 1.6-12.4). The median overall survival (OS) is 6.7 years with a median follow-up of 4.5 years. The median OS has not been reached for patients achieving a hematologic CR but exceeds 12.4 years, compared to 5.9 years for those not achieving CR (log-rank p<0.001). The median OS for patients following hematologic relapse is 3.5 years. Twenty-five % of patients are alive, up to 19 years after undergoing HDM/SCT. These data highlight the remarkable long-term survival results that can be obtained in patients with AL amyloidosis treated with HDM/SCT. While survival is strongly dependent upon achieving a hematologic CR, the survival of patients who do not achieve a CR and of those who relapse after CR also is notable, suggesting a benefit of treatment. Strategies to improve risk-stratification of patients and reduce TRM, as well as using sequential or combination therapies to increase the CR rate, will likely improve outcomes in the future for patients who just a few years ago were considered to have a rapidly fatal diagnosis. 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.

Phase III Randomized Stem Cell Mobilization Trial Comparing Standard Vs Double-Dose G-CSF Vs Standard Doses of G-CSF Plus GM-CSF in Hard to Mobilize Patients Undergoing An Autologous Hematopoietic Stem Cell Transplant (HSCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3228-3228
Author(s):  
Elizabeth Berger ◽  
Christopher Seet ◽  
Mala Parthasarathy ◽  
Tulio Rodriguez ◽  
Scott E. Smith ◽  
...  
Keyword(s):  
Stem Cell ◽  
Standard Dose ◽  
Stem Cell Mobilization ◽  
Phase Iii ◽  
Control Group ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Cell Mobilization

Abstract Abstract 3228 Poster Board III-165 Introduction Using standard dose G-CSF (10 μg/kg) for stem cell mobilization, 25-40% of patients, deemed to be hard to mobilize based on prior therapy, will not collect sufficient HSC (> 2-2.5 × 106 CD34/kg) to proceed to a prompt autotransplant. Strategies to improve CD34/kg yields have included dose escalating G-CSF up to 30 μg/kg or combining G-CSF and GM-CSF. While dose escalated G-CSF is effective in increasing CD34 yields in normal donors as is the combination of G-CSF and GM-CSF, their comparative value in pre-treated patients has not been tested. To determine the value of these strategies, we performed a randomized comparison of high dose G-CSF (30 μg/kg as 2 doses 12 hours apart), to the combination of simultaneous single daily doses of G-CSF (10 μg/kg) plus GM-CSF (5 μg/kg), to a control group receiving G-CSF at an equivalent total dose of cytokine to the combination arm (15μg/kg) as a single dose. Patients and Methods Patients were eligible if heavily pre-treated, defined as: a minimum of 10 total cycles of combination chemotherapy and two prior regimens, or a total of 6 chemotherapy cycles if the patient also received RT to marrow bearing sites, platinum-based chemotherapy or 2 or more cycles of any BCNU or fludarabine containing regimen. Baseline WBC had to be > 3000/μl, ANC > 1500/μl and a platelets > 100,000/μl. Twelve liter aphereses began on day 5 of mobilization, and continued until ≥ 4 × 106 CD34/kg were collected or a maximum of 5 aphereses. Patients typically proceeded to transplant if they had ≥ 2.5 × 106 CD34/kg collected and were always re-mobilized if they collected < 2.0 × 106 CD34/kg. CD34 subsets (CD34+/CD33- and CD34+/CD38-) were also assessed for the 3 groups to determine if more primitive HSC were mobilized by the 2 novel strategies. The sample size was calculated based as follows: 60% of the control group would collect 2.5 × 106 CD34/kg and this would rise to 90% in one or both study arms. The detection of such differences with a power of 80% and a 2-sided alpha level of 0.025 required a total sample of 120 patients. Results A total of 120 patients were randomized; 119 were eligible. Patient demographics, shown in the Table, were matched among the three groups: The % of patients collecting ≥2.5 × 106 CD34/kg was: standard G: 60%, high dose G: 57% (p = 1.0), G + GM: 41% (p = 0.1). Median CD34 collected in first mobilization were, 3.6 × 106/kg, 3.0 × 106/kg (p = 0.22) and 2.0 × 106/kg (p = 0.05) respectively in a median of 4, 4, and 5 aphereses (p = NS). Re-mobilization rates: standard G; 37.5%, high dose G: 35%; G + GM: 50% (p = NS). Total median CD34 collected from first and any second mobilizations were: standard G: 4.8 × 106/kg, high dose G: 3.9 × 106/kg, and G + GM: 3.5 × 106/kg. One patient in the standard G arm and 3 in high dose G did not proceed to transplant due to poor initial mobilization and progression in 2, and one each for progression or poor mobilization alone. There were no significant differences in median engraftment times: for ANC, 10, 11 and 15 days respectively for the standard G-, high dose G- and G + GM arms and for platelets, 11, 13 and 14 days respectively. The overall survivals @ the median f/u time of 37 months were 59.8%, 61.8% and 48.1% respectively (p = 0.272) for the three groups. The % primitive HSC (CD34+/CD33- and CD34+/CD38-) from the first mobilization were identical in the 3 patient groups. Conclusions We found no advantage to dose escalated G-CSF nor to the combination of G-CSF and GM-CSF to mobilize HSC for autotransplantation in heavily pre-treated patients. We also did not find higher numbers of more primitive CD34 subsets mobilized by these newer strategies. Alternative approaches, e.g. the combination of plerixifor + standard dose G-CSF (Stiff et al: BBMT; 15:249-56, 2009) would appear to be the preferred method of initial HSC mobilization for heavily pre-treated patients. Disclosures Stiff: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Stem Cell Mobilization after Various Induction Regimens in Patients with Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5433-5433
Author(s):  
Jakub Radocha ◽  
Vladimir Maisnar ◽  
Miriam Lanska ◽  
Jiri Hanousek ◽  
Katerina Machalkova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Conflicts Of Interest ◽  
Rapid Development ◽  
Autologous Transplantation ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Cell Transplant ◽  
Cell Mobilization ◽  
Stem Cell Collection

Abstract Stem cell mobilization after various induction regimens in patients with multiple myeloma Introduction: Rapid development of novel therapies for multiple myeloma has led to a significant improvement in response to the treatment. Stem cell mobilization before autologous stem cell transplantation is a source of considerable costs of transplant procedure. Whether modern induction regimens affect outcome of stem cell mobilization has not been extensively studied. Aim: The goal of this study was to compare efficacy of stem cell mobilization after different induction regimens in patients with multiple myeloma. The primary goal was to compare CTD (cyclophosphamide, thalidomide, dexamethasone), CVD (cyclophosphamide, bortezomib, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) and regimens in terms of succesful stem cell collection. Methods: All patients with multiple myeloma who have been planned for stem cell collection and were treated with one of the above mentioned regimens were included in this retrospective analysis. The demographic data, amount of stem cells collected, number of days needed to reach the target collection were recorded. All patients received high dose cyclophosphamide 2,5 g/m2 prior to stem cell collection and were primed with G-CSF twice daily from day 5. The collection was started at day 10. Collection goal was 8x106/kg CD34+ cells. Results: 15 patients received CTD, 25 patients CVD and 16 patients VTD regimen before stem cell collection. Groups were comparable according to age, gender and myeloma stages. Mean collected cells at the end of collection were 9.2 (SD 2.8) for CTD, 12.3 (SD 5.6) for CVD and 10.1 (SD 2.1) for VTD (p=0.066). Mean daily harvest was 3.4, 8.0 and 7.6 x106/kg respectively (p=0.01). Mean days needed to reach desired harvest were 3, 2.25 and 1.6 days (p=0.001). No collection failure was observed. Conclusion: The best collection results were seen in patients after induction with CVD or VTD regimen. VTD regimen also required the least days for collection and seems to be most beneficial for cost of collection. CTD regimen shows the least efficacy in stem cell collection before autologous transplantation. All patients managed to harvest for at least one stem cell transplant. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Treatment of AL Amyloidosis with Tandem Cycles of High Dose Melphalan and Autologous Stem Cell Transplantation: Final Analysis of a Prospective Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 612-612
Author(s):  
Vaishali Sanchorawala ◽  
Daniel G. Wright ◽  
Karen Quillen ◽  
Laura M. Dember ◽  
John L. Berk ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Improvement ◽  
Plasma Cell ◽  
Initial Treatment ◽  
Performance Status ◽  
Prospective Trial ◽  
Plasma Cell Dyscrasia ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant

Abstract AL amyloidosis is caused by a clonal plasma cell dyscrasia and is characterized by widespread, progressive amyloid deposition leading to multisystem organ failure and death. In this disease, amyloid protein deposits are derived from monoclonal immunoglobulin light chains. Aggressive treatment of AL amyloidosis with high dose intravenous melphalan followed by autologous stem cell transplant (HDM/SCT) is effective in inducing hematologic remission and clinical improvement. Furthermore, we have observed in over 300 patients treated with HDM/SCT that achievement of a hematologic complete response (CR), i.e. disappearance of monoclonal gammopathy and clonal plasma cell dyscrasia, is a critical determinant of clinical improvement and prolonged survival. Because of the importance of hematologic CR in treatment outcome, we conducted a prospective trial to determine whether a second cycle of HDM/SCT would induce a hematologic CR in patients in whom the plasma cell dyscrasia persisted following initial treatment with HDM/SCT. Additional objectives of the trial were to determine the feasibility and tolerability of tandem cycles of HDM/SCT in AL amyloidosis. Eligibility for entry into the trial required evidence of plasma cell dyscrasia, age &lt; 65 years, ≤ 300 mg of prior oral melphalan, and minimal measures of performance status (SWOG ≤ 2) and cardiopulmonary function (LVEF &gt; 45%, DLCO &gt; 50%). Peripheral blood stem cells were collected by leukapheresis following G-CSF mobilization, with minimum yields of 7.5 x 106 CD34+ cells/kg required for participation in the trial. From 11/2000 to 6/2005, 62 patients, median age 55.5 (range 32–65), M: F ratio 1.8:1.0, were enrolled. Of the 62 patients enrolled, 9 (15%) were removed from the protocol either because of an inadequate stem cell collection (7) or because of complications during stem cell mobilization and collection that precluded treatment with HDM/SCT (2). Of the 53 patients who received the first cycle of 200 mg/m2 HDM, 4 patients died within 100 days of treatment (8%), and 27 (55%) were found to have achieved a hematologic CR 6 months after HDM/SCT. Of the 22 patients who did not achieve a CR after initial treatment, 17 patients received a second HDM/SCT with 140 mg/m2 of IV melphalan. Mortality within 100 days after this second treatment was 6% (1/17), while 27 % (4/15) of surviving patients achieved a hematologic CR by 6 months following the second cycle of HDM/SCT. Therefore, for the patients treated with one or two cycles of HDM/SCT on this study, the ultimate hematologic CR rate was 63% (31/49). With a median follow up of 38 months (range, 14–69 months), the median survival for all patients enrolled has not yet been reached. Moreover, improvements in amyloid related organ dysfunction, particularly in nephrotic syndrome, liver involvement, neuropathy and/or performance status, were evident in all patients who achieved a hematologic CR. In conclusion, tandem cycles of HDM/SCT are tolerable for selected patients with AL amyloidosis and can increase the proportion of patients who ultimately achieve a hematologic CR.

Outcomes of tbo-filgrastim, filgrastim-sndz or filgrastim for mobilization in patients undergoing an autologous hematopoietic stem cell transplant: A single center experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19000-e19000
Author(s):  
Klodiana Neme ◽  
David Henkin ◽  
Nancy Mikulandric ◽  
Meredith Grycki ◽  
Angela Michael ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Stem Cell Mobilization ◽  
Hospital Length Of Stay ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Cell Mobilization

e19000 Background: Studies have reported that use of filgrastim (G) or any biosimilar result in similar stem cell yield during hematopoietic stem cell mobilization, but little is known on the effect of these biosimilars on length of hospitalization for the transplant procedure, engraftment, and long term survival of autologous hematopoietic stem cell transplant (HSCT) patients. Beginning January 2017, the Henry Ford Cancer Institute (HFCI) began utilizing tbo-filgrastim (TBO) and filgrastim-sndz (SNDZ) as part of mobilization. This study was conducted to evaluate transplant specific outcomes in HSCT patients comparing biosimilar and reference filgrastim products. Methods: This study retrospectively evaluated all patients treated at HFCI who received G-CSF based mobilization for HSCT between 1/2017 and 11/2018. Patient-, mobilization- and transplant specific variables were collected and analyzed. Results: A total of 113 patients underwent stem cell mobilization followed by collection and autologous HSCT. Of the 73 patients analyzed, 62% had a diagnosis of Multiple Myeloma (MM), 22% had Non-Hodgkin Lymphoma (NHL). Approximately 45% of patients received TBO, 44% received G and remainder received SNDZ. The percentage of patients who proceeded to HSCT was 86%. There was no difference in adequate CD34+ yield among the three G-CSF products (P = 0.074). There was no difference in mobilization associated complications including bone pain and thrombocytopenia. Plerixafor use was similar among the groups (P = 0.55). Actual CD34+ (P = 0.31) and the number of apheresis sessions required to collect an adequate CD34+ yield (P = 0.30) were not different among the groups. No significant differences were noted in time to neutrophil (P = 0.96) or platelet engraftment (P = 0.91) and hospital length of stay (P = 0.78). We found similar rates of infection, febrile neutropenia, and mucositis among the three groups. Relapse rates were also similar among the groups. Conclusions: In our institution transplant related outcomes were similar among patients who received TBO, SNDZ, and G as part of their pre-transplant mobilization protocol.

Non-Myeloablative vs. Conventional Allogeneic Hematopoietic Stem Cell Transplantation for Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1132-1132
Author(s):  
Brad Pohlman ◽  
Tao Jin ◽  
Elizabeth Kuczkowski ◽  
Stacey Brown ◽  
Ronald Sobecks ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
High Dose ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem

Abstract Non-myeloablative allogeneic stem cell transplantation (NMT) is increasingly used as an alternative to conventional bone marrow transplantation (BMT). Limited NMT data is available for lymphoma patients (pts). Most series include all hematological malignancies and only a minority with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL). Therefore, we reviewed the Cleveland Clinic BMT Program experience with lymphoma pts and specifically compared the outcome between NMT and BMT. Between July 2, 1985 and December 7, 2004, 67 pts received a matched related (n=47) or unrelated (n=20) donor BMT (n=46) or NMT (n=21) for HL (n=11), aggressive NHL (n=32), indolent NHL (n=23), or unknown NHL (n=1). Pts with lymphoblastic, Burkitt, or atypical Burkitt-like lymphoma were excluded. Compared to BMT pts, NMT pts were older, had longer time from diagnosis to transplant (tx), and were more likely to have a normal LDH and be in remission (CR/PR) at tx. The median follow-up of surviving BMT and NMT pts was 73.8 (range 11.8–106.7) and 20.6 (range 2.8–44.0) months, respectively. 18 (39%) BMT and 5 (24%) NMT pts progressed, and 9 (20%) BMT and 2 (10%) NMT pts died from lymphoma. The incidence of grade 2–4 acute GVHD was not different between the BMT and NMT groups. Among all pts, the risk of lymphoma progression was significantly higher in pts with compared to pts without GVHD (Figure 1). The overall survival for NMT pts was significantly better than for BMT pts (P=.019). Among 15 pts that previously received high dose therapy with autologous stem cell transplant (ASCT), all 7 BMT pts died a median of 1 (range 1–14) month post-BMT while 4/8 NMT pts remained alive 8, 21, 29, and 33 months post-NMT. By multivariate analysis, BMT (HR 7.74, 95% CI 2.49–24.0, P&lt;.001), HL (HR 6.52, 95% CI 2.04-20-85, P=.002), prior ASCT (HR 3.33, 95% CI 1.20–9.25, P=.021), and increasing age by decade (HR 1.7, 95% CI 1.11–2.62, P=0.14) were associated with a significantly higher mortality while CR/PR at tx was associated with a significantly lower mortality (HR 0.44, 95% CI 0.21–0.93, P=.032). Restricting the multivariate analysis to the 56 NHL pts identified no significant independent prognostic factors. Finally, excluding the 15 pts with prior ASCT showed that BMT, &gt;3 prior chemotherapy regimens, tumor &gt;10 cm at diagnosis, older age, and no remission at tx were all associated with a significantly higher mortality. We conclude that: 1) lymphoma progression and lymphoma- or transplant-related death beyond 2 years are uncommon; 2) BMT after failed ASCT is uniformly fatal while NMT (even after failed ASCT) may lead to long-term survival; 3) GVHD (with its presumed graft vs. lymhoma effect) is important for long-term, progression-free survival; 4) compared to BMT, NMT is associated with a better OS (although pt selection may account for some of the observed difference), and 5) both NMT and BMT are appropriate options for selected NHL pts. Whether NMT or BMT offers any benefit compared to ASCT for HL pts is unclear. Figure Figure

Long Term Survival Analysis after High-Dose Melphalan Chemotherapy Followed by Autologous Stem Cell Transplantation for Treatment of AL Amyloidosis: A Single Centre Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5503-5503
Author(s):  
Jolanta B. Perz ◽  
Amin Rahemtulla ◽  
Chrissy M. Giles ◽  
Richard Szydlo ◽  
Jane F. Apperley
Keyword(s):  
Stem Cells ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
High Dose ◽  
Al Amyloidosis ◽  
Term Survival ◽  
High Dose Melphalan

Abstract Introduction: AL amyloidosis (AL) is a clonal plasma cell disease with a median survival of 10–14 months without therapy. Phase II studies report remission rates in up to 50% of patients (pts) after high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT). We retrospectively analysed AL pts who underwent HDM and ASCT at the Hammersmith Hospital in London since 1996. Patients and methods: 19 pts (12 m, 7 f), median age 51 y (40 – 63 y) with lambda (14) or kappa (5) AL (2 pts with multiple myeloma stage IA) had the following leading organ involvements: 10 kidney, 3 cardiac, 3 liver or gut, 3 other. 12 pts had more than 2 involved organs. According to risk criteria for HDM (Comenzo and Gertz, 2002) 12 pts were high, 2 pts intermediate and 5 pts low risk. Stem cells were mobilised with Cyclophosphamide (4 g/m2) in 3 pts, Etoposide (1.6 g/m2) in 1 patient, G-CSF alone in 14 pts, 1 bone marrow harvest was performed. Melphalan dose was: 8 pts 200 mg/m2, 5 pts 140 mg/m2, 6 pts 100 mg/m2. The median number of infused stem cells was 3.45 x 106 CD 34+ /kg bw (1.96 – 11.3 x 106 CD 34+ /kg bw). Results: Treatment related mortality (TRM) was 26%. In 14 patients who survived longer than 100 days from ASCT 6 pts achieved a haematological remission (5 a complete remission, 1 a partial remission) but in 8 patients no remission was achieved: 2 pts received a second ASCT, 2 pts further chemotherapy, 2 pts required haemodialysis. The mean survival from HDM and ASCT is 58.1 months (SD 9.64 months, 95% CI 39.21 – 76.99). The 1 - year and 2 - years overall survival from HDM and ASCT was 73% and 62%, respectively. The overall survival dropped to 42% after 6 years and the main cause of death was progressive or relapsed AL. Conclusions: HDM and ASCT is feasible for patients with AL, however, TRM was high at 26% in a group of maily high risk patients. 62% of patients survived longer than 2 years, but disease relapse and deaths from relapsed or progressive disease occurred after longer than 2 years from HDM. Thus, new treatment strategies have to be investigated to treat disease progress and relapse in order to improve the long-term survival after HDM and ASCT in patients with AL.

Hypercholesterolemia and Its Association with Enhanced Stem Cell Mobilization and Harvest After High-Dose Cyclophosphamide + G-CSF

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2247-2247
Author(s):  
Martina Crysandt ◽  
Ralf-Dieter Hilgers ◽  
Sabine von Hobe ◽  
Albrecht Eisert ◽  
Edgar Jost ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Prior Therapy ◽  
Cholesterol Levels ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 2247 Hematopoietic stem cells (HSC) reside in specific niches in the bone marrow and various signals regulate survival, self-renewal, proliferation, differentiation and trafficking. Egress of HSCs into the peripheral blood (PB) is enhanced by multiple agonists, although the exact mechanisms that regulate this critical process are largely unknown. After treatment with cyclophosphamide and G-CSF, long-term HSC in the bone marrow enter the cell cycle. Additionally, G-CSF induces a reduction of the chemokine stromal cell derived factor 1 (SDF-1) and an increase of its receptor CXCR4 in the bone marrow leading to mobilization of HSC to the PB. Very recently, hypercholesterolemia was identified to promote stem cell mobilization in mice by also disrupting the SDF-1/CXCR4 axis. We retrospectively examined the role of cholesterol and a number of possible confounding factors on mobilization results and stem cell harvests in a patient cohort undergoing a standard mobilization procedure. We retrospectively identified 104 patients receiving high-dose cyclophosphamide (CY) for stem cell mobilization between 1997 and 2009 using a clinical database. We examined the role of cholesterol and a number of additional possible confounding factors (e.g. gender, weight, age, number of prior therapy lines, laboratory results like creatinine, uric acid, bilirubin, potein, LDH and long-term medication with common drug classes) on stem cell mobilization and harvest using univariate and multivariate analyses. Out of the 104 patients, 21 did not have cholesterol levels available. Among the remaining 83 patients included, 33 (39.8%) were identified as having hypercholesterolemia (defined as >6.2 mmol/L). The mean number of prior lines of anti-neoplastic therapy was 1.52 (median 1, range 1–6). A lower number of prior therapy lines (p=0.010), higher lactate dehydrogenase levels (LDH, p=0.006), higher cholesterol (p=0.012) and triglycerides (TG, p=0.041) as well as long-term medication with beta-blockers (p=0.024) were significantly correlated with better CD34+-mobilization. Since, as expected, cholesterol and TG were highly correlated (p<0.001), TG were excluded from further multivariate analysis as a single factor. A multivariate ANCOVA model then allowed the adjusted assessment of the influencing factors on the peak CD34+-counts and revealed a positive linear dependence on LDH (slope: 0.41, p=0.047) and on cholesterol (slope: 0.60, p=0.012) only. Patients with hypercholesterolemia had a higher CD34+-peak compared to patients with normal cholesterol levels (135.5 vs. 73.4/μL, p=0.015). The mean CD34+-cell counts in the PB showed significantly higher levels on day 12 (109.1 vs. 53.8/μL, p=0.033) and on day 13 (123.7/μL vs. 45.7/μL, p=0.002). This clinical data is in high accordance with data in the mouse model that could show a major effect of a high-cholesterol diet on the number of circulating progenitor cells. Accordingly, the overall number of harvested CD34+-cells was higher in patients with hypercholesterolemia (1027.5 vs. 644.4×106, p=0.039, adjusted to body weight: 14.7 vs. 8.5×106/kg, p=0.060) and a sufficient number for at least one stem cell transplantation (more than 2.0 CD34+ cells × 106/kg) was achieved in a remarkably higher proportion (84.9%vs. 52.9%, p=0.004). In summary, our retrospective multivariate analysis including multiple possible factors extends this significant and potentially clinically relevant observation to the human system, since patients with hypercholesterolemia showed better mobilization, higher stem cell yields and a sufficient harvest for at least one autologous transplantation in a remarkably higher proportion. Whether in patients with successfully treated hypercholesterolemia, cholesterol-lowering therapy should be stopped during mobilization therapy in order to increase stem cell harvest will need to be assessed in the context of a clinical trial following prospective validation of the results reported here. Furthermore, it remains to be seen whether this effect is still preserved under stem cell mobilization with other regimens such as plerixafor. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem-cell transplantation

Blood ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 3561-3563 ◽  
Author(s):  
Vaishali Sanchorawala ◽  
Martha Skinner ◽  
Karen Quillen ◽  
Kathleen T. Finn ◽  
Gheorghe Doros ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Survival ◽  
High Dose ◽  
Al Amyloidosis ◽  
Term Survival ◽  
Long Term Outcome ◽  
High Dose Melphalan

AbstractLong-term survival and outcome were determined for 80 patients with immunoglobulin light chain (AL) amyloidosis treated with high-dose melphalan and stem cell transplantation (HDM/SCT) more than 10 years ago. Seventeen (21%) patients died within the first year of treatment, of treatment-related complications (14%) or progressive disease (8%). Of the 63 surviving evaluable patients at one year, 32 (51%) achieved a complete hematologic response (CR). For all 80 patients, the median survival was 57 months (4.75 yrs). The median survival exceeds 10 years for patients achieving a CR after HDM/SCT, compared with 50 months for those not achieving a CR (P < .001). In conclusion, HDM/SCT leads to durable remissions and prolonged survival, particularly for those patients who achieve a hematologic CR.

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