Increased Bone Marrow Plasma Cell Infiltration Pre-Transplant Is Associated with Worse Outcomes in Patients Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplantation for Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4135-4135
Author(s):  
Nina Shah ◽  
Qaiser Bashir ◽  
Simrit Parmar ◽  
Yvonne T Dinh ◽  
Sofia Qureshi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Plasma Cell ◽  
Progressive Disease ◽  
Patient Characteristics ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
High Group

Abstract Abstract 4135 Multiple myeloma (MM) is the second most common adult hematologic malignancy. High dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) have become the standard of care for eligible patients. Though the impact of bone marrow (BM) plasma cell (PC) percentage has been explored in the post-SCT setting, its role before SCT is not yet known We performed a retrospective review of 1826 MM pts who underwent HDC and auto-SCT at our institution from 7/8/98 – 12/31/2010. We further identified patients who had post-induction, pre-SCT BM biopsy information available. Patients were divided into 2 groups: those with <10% PC infiltration (“PC low”) and those with ≥10% plasma cell infiltration (“PC high”). Additional data, such as demographics, time of diagnosis, response, time to progression and time of death were also collected. Progression-free (PFS) and overall (OS) survivals were estimated by the Kaplan-Meier method. Log-rank test was performed to test the difference in survival between groups. 1489 pts were studied, 605 female and 884 male. Patient characteristics are detailed in Table 1. Median time from diagnosis to auto-SCT was 247 days (range 45–7895). 1299 (87%) patients underwent auto-SCT after 2000. Nearly all patients received melphalan-based conditioning. 1174 patients had <10% involvement of BM by PCs and 315 had > 10% involvement. The details of best responses before and after auto-SCT are also listed in Table 1. For patients in the PC low group, 32% had a CR, 20% had a VGPR, 31% had a PR, 13% had <PR and 3% had progressive disease after auto-SCT. For patients in the PC high group, 11% had a CR, 14% had a VGPR, 48% had a PR, 21% had <PR and 5% had progressive disease (PD) after auto-SCT. Median PFS was significantly shorter for the PC high group versus the PC low group (24.8 vs 29.5 months, p=0.05), as was median OS (52.5 vs 79.4 months respectively, p<0.001). When only those patients who had a PR to induction were examined, there was again a significant difference in both PFS (24.4 vs 33.2 months, p=0.04) and OS (58.3 vs 81.2 months, p =0.002) for those patients in the PC high versus PC low groups, respectively. Finally, when looking at those patients who underwent auto-SCT in the era of novel therapeutics (after 2000), the differences between the PC high and PC low groups were maintained for both PFS (24.4 vs 29.5 months respectively (p=0.029)) and OS (54.8 vs 88.4 months respectively, p<0.001). Table 1. Patient characteristics and responses All patients (n=1489) PC <10% (n=1174) PC ≥ 10% (n=315) Male 884 (59%) 718 (61%) 166 (53%) Female 605 (41%) 456 (39%) 149 (47%) Race 988 (66%) 784 (67%) 204 (65%) Caucasian 230 (15%) 181 (15%) 49 (16%) African American 33 (2%) 24 (2%) 9 (3%) Asian Unknown/other 238 (16%) 185 (16%) 53 (17%) Durie-Salmon Stage (1440 pts)     I 218 (15%) 179 (16%) 39 (13%)     II 597 (41%) 486 (43%) 111 (37%)     III 626 (43%) 472 (42%) 154 (51%) Cytogenetics (1265) Normal 943(75%) 782 (79%) 161 (58%) Abnormal 322 (25%) 207 (21%) 115 (42%) Response prior to auto-SCT     CR 66 (4%) 66 (6%) 0 (0%)     VGPR 255 (17%) 244 (21%) 11(3%)     PR 817 (55%) 655 (56%) 162 (51%)     <PR 232 (16%) 144 (12%) 88 (28%)     PD 93 (6%) 45 (4%) 48(15%)     unknown 26 (2%) 20 (2%) 6 (2%) Median time to SCT (range) 247 days (45–7895) 239 days (45–7895) 259 days (74–5580) SCT after 2000 1299 (87%) 1037 (88%) 262 (83%) Best response after SCT     CR 384 (26%) 350 (32%) 34 (11%)     VGPR 298 (20%) 253 (20%) 45 (14%)     PR 510 (34%) 359 (31%) 151 (48%)     <PR 223 (15%) 157 (13%) 66 (21%)     PD 45 (3%) 30 (3%) 15 (5%)     Not evaluable 29 (2%) 9 (1%) 4 (1%) PFS from SCT (months) 29.5 24.8 P=0.05 OS from SCT (months) 79.4 52.5 P<0.001 PR-PFS from SCT (months) 33.2 24.4 P = 0.04 PR- OS from SCT (months) 81.2 58.3 P = 0.002 Post-2000 SCT PFS from SCT (months) 29.5 24.4 P = 0.029 Post-2000 SCT OS from SCT (months) 88.4 54.8 P<0.001 Extensive BM infiltration by PCs before auto-SCT is associated with a worse outcome in patients treated with HDC and auto-SCT. This finding persists when looking specifically at patients with a PR before auto-SCT. Thus, BM disease burden may further assist us in stratifying patients with a PR and may warrant further disease reduction before stem cell collection. Additionally, the differences between PC high and PC low groups are maintained in the modern era, despite the availability of several new salvage agents over the last 10 years. Further prospective study is warranted to determine the true impact of PC infiltration in the BM. Disclosures: No relevant conflicts of interest to declare.

A Case of Multiple Myeloma(MM) with Myelofiblosis(MF) Undergone Autologous Peripherial Blood Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5496-5496
Author(s):  
Zhisheng Jiang ◽  
Shunjie Wu ◽  
Da Li ◽  
Qi Chen ◽  
Xinhao Lan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Bone Marrow Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Plasma Cell ◽  
Marrow Transplantation ◽  
High Dose ◽  
Myeloid Metaplasia

Abstract Myelofibrosis with myeloid metaplasia(MMM) is a progenitor cell colony disease. The mechanism is not very clean. The prognosis is poor in MMM patients of the traditional treatment with Hydroxyurea, Interferne, Prednisone, transfusion. Thalidomide is a new anti-angiogenesis drug of inhibiting the genesis of fibrosis. Some reports presented that the cure method only is stem cell transplantation includes autologous and allogeneic bone marrow transplantation. Patient Sui, Man, 55 years, Chinese. He was hospitalized on Aug fifth, 2004, because he has had pale, severe weakness, for 5 months. T 36.C, HR 70, R 18/min, BP114/59 mmHg. Hb56g/L, WBC 5.7x109/L, Plt 72 x109/L.There were 0.66 plasma cell in bone marrow and his bone marrow aspiration with dry draw at the diagnosis,. The result of bone marrow biopsy was fibrosis. He received 4 courses of VAD regimens (VCR 0.4mg,d1–4; ADM 10mg,d1–4, DXM 40mg d1–4) before autologous peripheral stem cell (PBSCs) transplantation. The plasma cell count decreased from 0.66 before to 0.025 after the first course of VAD regimen in the bone marrow. The stem cell mobilization regimen was chemotherapy (cyclophosphamide, Cy, 2g/m2), high-dose methylprednisolone (MP), and G-CSF 250 ug, bid d1–5. The nucleated cell count of collection showed the a minimum of 4.17x108/kg per kg of body weight, CD34+ was 0.834x106/kg.The conditional regimen was melphalan 200mg/kg divided 2 times a day and cyclophosphamide 600mg VD. He received re-transfused PBSCs on March 25,2005. His neutrophil cell decreased 0 at +4 day after transplantation. He received platelet transfusion of single donor two times when his platelet decreased 7 x 109/L. his hemotopoietic recovered at +11d. He left transplantation ward +13 d. His platelet, WBC were normal, Hb 108g/L At+d. Bone marrow draw was no dry. There was 0.07 of plasma cell in his bone marrow. The result of reticulum protein stain was degree 3 after and 4 before PBSCT at +70d. Discussion: MM is incurable tumor because the tumor cells polluted in graft of bone marrow or peripheral blood stem cells. Some author considered the pollution tumor cell decreases with high-dose MP mobilization. Mobilization of stem cell in advanced MMM is difficulty, so we (1) increased the 3 times of mobilization, (2) added high-dose of MP to mobilization regimen of combination of Cy and G-CSF. The patient had received pre-transplantation of four courses of VAD chemotherapy regimen and the combination of west and Traditional Chinese Medicine to manage during stem cell transplantation. The patient had chronic gastric ulcer so we afraid of the condition result in relapse of it so we given the patient intravenous melphalan. Some researchers studied 21 cases of multiple myeloma were treated by autologous bone marrow transplantation. The condition regimen was melphalan 16 mg/kg. The role of allogeneic BMT as compared with autologous BMT is not yet defined. The patient had been followed up for 4 months, the result showed his plasma cell was 0.07 in his bone marrow. The degree of myeloid metaplasia had changed from degree 4 to 2. Conclusion: Intensive treatment with marrow rescue could induce complete remission of long duration in some patients and provided the basis for increased attempts to cure myeloma by intentive chemoradiotherapy and BMT. It is effective in multiple myeloma treatment with autologous stem cell transplantation. The curable method is only allogeneic stem cell maybe.

166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2684-2691 ◽  
Author(s):  
Sergio Giralt ◽  
William Bensinger ◽  
Mark Goodman ◽  
Donald Podoloff ◽  
Janet Eary ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Phase 1 ◽  
High Dose ◽  
Two Phase ◽  
Hematopoietic Stem

Abstract Holmium-166 1, 4, 7, 10-tetraazcyclododecane-1, 4, 7, 10-tetramethylenephosphonate (166Ho-DOTMP) is a radiotherapeutic that localizes specifically to the skeleton and can deliver high-dose radiation to the bone and bone marrow. In patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation two phase 1/2 dose-escalation studies of high-dose 166Ho-DOTMP plus melphalan were conducted. Patients received a 30 mCi (1.110 Gbq) tracer dose of 166Ho-DOTMP to assess skeletal uptake and to calculate a patient-specific therapeutic dose to deliver a nominal radiation dose of 20, 30, or 40 Gy to the bone marrow. A total of 83 patients received a therapeutic dose of 166Ho-DOTMP followed by autologous hematopoietic stem cell transplantation 6 to 10 days later. Of the patients, 81 had rapid and sustained hematologic recovery, and 2 died from infection before day 60. No grades 3 to 4 nonhematologic toxicities were reported within the first 60 days. There were 27 patients who experienced grades 2 to 3 hemorrhagic cystitis, only 1 of whom had received continuous bladder irrigation. There were 7 patients who experienced complications considered to be caused by severe thrombotic microangiopathy (TMA). No cases of severe TMA were reported in patients receiving in 166Ho-DOMTP doses lower than 30 Gy. Approximately 30% of patients experienced grades 2 to 4 renal toxicity, usually at doses targeting more than 40 Gy to the bone marrow. Complete remission was achieved in 29 (35%) of evaluable patients. With a minimum follow-up of 23 months, the median survival had not been reached and the median event-free survival was 22 months. 166Ho-DOTMP is a promising therapy for patients with multiple myeloma and merits further evaluation. (Blood. 2003;102:2684-2691)

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