Hirsutism will be not Considered as Sign of Progressive Disease after Autologous Transplant in POEMS Syndrome

Abstract Abstract 3146 Background: High dose chemotherapy and stem cell transplantation (HDSCT) has been a standard of care for younger patients with adequate organ function since the early 1980s, due to its superiority over standard chemotherapy in prolonging disease-free and overall survival. Immunomodulatory agents, including thalidomide and lenalidomide, have significant single-agent activity and an additive effect when combined with melphalan. Preclinical data suggest an increased DNA damage and an anti-angiogenic effect with the combination. Additive clinical benefits were also observed when the 2 agents were used in combination in non-transplant settings. The antimyeloma effects of both agents are dose-dependent with myelosuppression being the dose limiting toxicity (DLT). This toxicity can be attenuated with stem cell rescue. Purpose: We conducted a phase I/II trial designed to evaluate the safety and efficacy of combining lenalidomide with high-dose melphalan as conditioning for autologous transplant for myeloma. The phase I portion of the study is complete and the results are reported in this abstract. Experimental Design: The enrolled patients included any patients with myeloma, regardless of the status of the disease, undergoing high dose melphalan for autologous stem cell transplantation. The melphalan dose was fixed (200 mg/m2) while the doses of lenalidomode were escalated from 50, 75, 100, and 150 mg/m2 administered orally days -7 to +2 of the transplantation. Dose escalation was based upon a 3+3 phase I design. DLTs were defined as grade ≥4, both hematologic and non-hematologic, occurring between days -7 to -2 which prevents subjects from undergoing stem cell transplantation, or grade 3 or 4 non-hematologic toxicity occurring after day -2 that does not resolve to a grade 2 or less by day +30 after transplantation, or delayed engraftment. The response was assessed at day +100 post transplantation using the International Myeloma Working Group criteria. Results: 13 patients participated in the phase I portion of the study from September 2010 to May 2012. Patients ages ranged from 42– 72 years (median 63 years). Seven patients were undergoing their first autologous transplant with 2 patients having had 2 lines of previous therapy and 5 having one line of therapy. Six patients were undergoing their second transplantationas salvage for control of progressive disease and all had more than 3 lines of prior therapy. At baseline, 5 patients had progressive disease, 1 had SD, 3 had PR, 3 had VGPR and 1 had CR as responses to their most recent lines of therapy. The median time for ANC and platelet engraftment was 10 days and no delayed engraftment was observed. Toxicities and posttransplant hematopoietic recovery rates were similar to historical data observed with single agent high dose melphalan. The most common grade ≥ 3 adverse events were myelosuppression, neutropenic fever and electrolyte abnormalities, all of which are commonly observed with single agent high dose melphalan. Adverse events related to the study drugs were electrolyte abnormalities (hypokalemia, hyperkalemia and hypocalcemia), gastrointestinal side effects and rash, all of which were grade 1 to 2 and manageable without a delay or discontinuation of the study drugs. One patient died from disease progression prior to scheduled disease evaluation. One patient has not yet reached day +100 post transplant. Therefore, responses were evaluable for 11 patients. Three patients achieved stringent CR (27%), 3 CR (27%), 2 VGPR (18%), 3 PR (27%) and one had progressive disease (9%). The overall response rate was 91%, with 72% achieving VGPR or better. All patients had adequate count recovery and were able to initiate lenalidomide maintenance treatment by day +100 to +110 post transplantation. Conclusions: The use of high dose lenalidomide in conjunction with high-dose melphalan is well tolerated, with preliminary data suggesting that the combination is highly efficacious. DLT was not observed; therefore the recommended phase II dose is 150 mg of lenalidomide orally on days -7 to +2 in combination with melphalan 200 mg/m2. The phase II portion of this trial is ongoing in patients undergoing first HDSCT. Complete response at 3 months post transplantation is the primary end point. Disclosures: Off Label Use: Lenalidomide in myeloma transplant. Abonour:Celgene: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau.

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High-Dose Therapy/Stem Cell Support (HDT), Including Tandem Transplant, for Primary Refractory Multiple Myeloma (MM): Results from the Spanish Myeloma Group (PETHEMA/GEM) in 49 Patients.

Blood ◽

10.1182/blood.v106.11.5472.5472 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5472-5472

Author(s):

L. Rosinol ◽

R. Garcia-Sanz ◽

J. J. Lahuerta ◽

M. Hernandez-Garcia ◽

A. Sureda ◽

...

Keyword(s):

Progressive Disease ◽

Intensive Therapy ◽

High Dose ◽

Refractory Disease ◽

High Dose Therapy ◽

Dose Therapy ◽

Autologous Transplant ◽

Number Of Patients ◽

Similar Survival ◽

Reduced Intensity

Abstract It is assumed that patients with primary refractory myeloma are the most likely to benefit from early HDT. In four series the CR rate was between 8 and 40% and the overall survival ranged from 4 to 6 years. However‚ the number of patients with progressive disease vs those with “stable disease” was not given in published series. The aim of our study was to investigate the efficacy in terms of response up-grading and survival of early HDT in patients with primary refractory myeloma. From October 1999 to December 2003 patients with MM younger than 70 years were given 6 courses of VBMCP/VBAD chemotherapy. Patients with refractory disease were scheduled to receive a tandem transplant‚ the first procedure intensified with busulphan-12 mg/kg-/melphalan-140 or melphalan-200 and the second with the CVB -cyclophosphamide‚ etoposide and BCNU- or with a dose-reduced intensity “allo” conditioned with fludarabine/melphalan-140‚ depending on sibling donor availability. Response and progression were defined according to the EBMT criteria. Forty-nine patients with primary refractory disease were identified. Twenty patients showed progression after their initial chemotherapy while 29 patients had “non-responding‚ non-progressive disease”. Eighty percent of the patients achieved some degree of response after the first autologous transplant (CR or near-CR: 8%‚ PR: 56%‚ MR: 16%) while 10% did not respond and 10% died from the procedure. Twenty-four patients were given a second transplant (autologous: 17‚ allogeneic: 7). Forty-six percent of the 17 patients who received a second autologous transplant upgraded their response (CR: 6%‚ PR: 17%‚ MR: 23%) while 41% had progressive disease or “no-change” and 13% died from the procedure. Three of the seven patients who underwent a dose-reduced intensity “allo” responded (2 CR‚ 1 PR) while two had progressive disease and two died from transplant-related complications. The median survival of the whole series of 49 patients was 32 months. Patients who had progressive disease after the initial chemotherapy had a significantly shorter survival than those who showed “non-responsive‚ non-progressive disease” (median 21 months vs. not reached‚ p=0.003). Finally‚ patients with “non-responding‚ non-progressive disease” had similar survival than those with chemosensitive disease intensified with HDT in the GEM trial. Conclusions. A high-dose therapy approach in patients with primary refractory myeloma results in a high overall response‚ but the CR rate is low‚ patients with progressive disease to the initial chemotherapy have short survival despite intensive therapy‚ and patients with “non-responding‚ non-progressive disease” have similar survival than chemosensitive patients. Whether the good outcome of the latter patients is mainly due the effect of HDT or to the natural history of a more indolent disease remains to be determined.

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Successful Salvage of High-Risk B-Cell Non-Hodgkin and Hodgkin Lymphoma with Double-Unit Cord Blood Transplantation Provides a Platform for Further Optimization

Blood ◽

10.1182/blood.v124.21.1258.1258 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1258-1258

Author(s):

Parastoo B Dahi ◽

Craig S. Sauter ◽

Sean M. Devlin ◽

Marissa N Lubin ◽

Doris M. Ponce ◽

...

Keyword(s):

High Risk ◽

Cord Blood ◽

B Cell ◽

Hodgkin Lymphoma ◽

Cumulative Incidence ◽

Research Funding ◽

Progressive Disease ◽

Autologous Transplant ◽

Day Range ◽

Grade Ii

Abstract Introduction: Allogeneic transplantation using double-unit cord blood grafts (DCBT) is an alternative therapy for adult patients with high-risk lymphomas without a HLA-matched sibling or volunteer donor but the efficacy of DCBT in this setting is not established. Methods: We analyzed overall survival (OS) and progression-free survival (PFS) after 4-6/6 HLA-matched DCBT in adults with B-cell non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) who were transplanted 2/2006-5/2013. Results: Patient characteristics by diagnosis are shown in the Table. Overall, the 47 patients (median age 46 years, range 20-70) had a median number of prior treatment regimens of 4 (range 1-13), 22/47 (47%) patients had had a prior autologous transplant, and the median pre-transplant HCT-CI score was 2 (range 0-6). Twenty-eight (60%) were in complete remission (CR). Conditioning was reduced intensity (RI) but functionally myeloablative in 16 patients (8 Cy/Flu/Thio/TBI400, 8 Mel/Flu) and 31 patients received non-myeloablative conditioning (NMA, Cy/Flu/TBI200). CB units had a median infused TNC dose x 107/kg of 2.7 (range 1.5-4.3) for the larger unit and 1.9 (range 0.9-3.4) for the smaller unit and a median donor-recipient HLA-allele match of 5/8 (range 1-7). The cumulative incidence of donor-derived engraftment was 98% (95%CI:77-99) with a median 22 day (range 13-37) and 10 day (range 7-46) neutrophil recovery after RI and NMA conditioning, respectively. Day 100 grade II-IV acute GVHD (20 grade II, 7 grade III, 1 grade IV) and 1-year chronic GVHD were 61% (95%CI:45-74) and 17% (95%CI:8-29), respectively. Day 180 transplant-related mortality (TRM) was 17% (95%CI:8-29). To date, 11 patients have progressive disease (median 3.4 months, range 2.8-58.0). The 3-year cumulative incidence of progression was 22% (95%CI:11-34). With a median 60 month (range 15-101) follow-up of survivors, the 3-year KM estimate of OS and PFS are 56% (95%CI:44-73) and 44% (95%CI:31-61), respectively (Figure). Of 23 patients who have died, 7 died of progressive disease whereas 16 died of transplant complications (2 organ failure, 10 GVHD, 2 infection, 1 encephalopathy of unknown cause, and 1 donor leukemia). Best PFS was observed in patients with follicular NHL (3-year PFS 62%) followed by HL (3-year PFS 47%) whereas those with diffuse large B-cell lymphoma, for example, did poorly (Table). There was no differences in 3-year PFS according to recipient age, HCT-CI, or number of prior regimens (each split above versus below the median), or receipt of a prior autologous transplant (all p = NS). Similarly, patients in CR pre-CBT (n = 28) had a 3-year PFS of 42% as compared to a 46% PFS in the non-CR patients (n = 19), p = 0.568. Four of 11 patients who relapsed survive to date (range 29-81 months) after treatment with chemotherapy (n = 3) or subsequent CB-derived mobilized peripheral blood stem cell (PBSC) transplant (n = 1). Conclusions: PFS after DCBT in patients with follicular NHL and HL is similar to that of adult donor allograft series and warrants further investigation. However, DCBT in other histologies is not as favorable. The high TRM rates may be influenced by the extent/intensities of prior therapy. Future clinical trials with DCBT should focus on strategies to reduce TRM, especially related to GVHD. Post-transplant maintenance to prevent disease progression could also be beneficial. Finally,chemotherapy to treat post-CBT relapse and CB-derived PBSC transplant are potential therapeutic options in selected patients. Table DiseaseType(N) Median(range) age Median(range)HCT-CI Remission status Median (range) prior regimens /N prior auto Regimenintensity PFS Follicular (n = 13) 52 yrs (29-63) 1 (0-4) 5 CR, 5 PR, 3 SD 4 (2-8) / 3/13 (23%) 3 MA 10 NMA 3-yr: 62% (95%CI: 40-95) Diffuse large cell (n = 13) 53 yrs (35-64) 2 (0-6) 8 CR, 4 PR, 1 SD 4 (1-7) / 3/13 (23%) 4 MA 9 NMA 3-yr: 23% (95%CI: 9-62) Mantle cell (n = 5) 57 yrs (37-71) 2 (1-6) 5 CR 3 (2-4) / 4/5 (80%) 5 NMA 2 disease-free at 29-70 months Hodgkins (n = 15) 35 yrs (20-50) 3 (0-5) 10 CR, 3 PR, 1 SD, 1 PD 4 (2-13) / 12/15 (80%) 8 MA 7 NMA 3-yr: 47% (95%CI: 27-80) T-cell rich B-cell NHL (n = 1) 38 yrs 2 PR 7 / No auto 1 MA Died at 1.5 months Figure 1 Figure 1. Disclosures Moskowitz: Merck: Research Funding; Genentech: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding.

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Progressive disease after high-dose therapy and autologous transplantation for lymphoid malignancy: clinical course and patient follow-up

Blood ◽

10.1182/blood.v80.8.2142.2142 ◽

1992 ◽

Vol 80 (8) ◽

pp. 2142-2148 ◽

Cited By ~ 119

Author(s):

JM Vose ◽

PJ Bierman ◽

JR Anderson ◽

A Kessinger ◽

J Pierson ◽

...

Keyword(s):

Bone Marrow ◽

Median Survival ◽

Progressive Disease ◽

High Dose ◽

Lymphoid Malignancy ◽

High Dose Therapy ◽

Durable Response ◽

Dose Therapy ◽

Autologous Transplant ◽

Short Period

Abstract Of 364 patients with lymphoid malignancy who underwent high-dose therapy with autologous bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PSCT), 169 patients have had progressive disease after the procedure. The median survival from the time of relapse for patients with Hodgkin's disease (HD) who progressed after the transplant was 10.5 months. This compares with a median survival of 3 months for relapsed non-Hodgkin's lymphoma (NHL) patients (P = .0036). After failing transplantation, 56 patients were treated with further chemotherapy, 35 with involved field irradiation therapy, and 18 patients were treated with combination chemotherapy and irradiation. Seven patients received biologic therapy and seven patients underwent a second bone marrow transplant. The remainder of the patients were believed to be too ill for further therapy or chose not to receive further treatment for their recurrent lymphoid malignancy. Sixty of the 169 patients with progressive disease after the transplant are still alive; however, only 18 patients are alive off therapy without evidence of active disease after their relapse. Ten of the 18 patients are still less than 12 months past their posttransplant salvage therapy and are at high-risk for relapse. Five patients are progression free at 15 to 36 months after their posttransplant relapse. Only three patients (two NHL and one HD) treated with other modalities after autologous transplant failure are alive without evidence of disease and have been observed at least 4 years postrelapse. Although a few patients will have a durable response to subsequent therapy, the majority of patients who have progressive disease after an autologous transplant for lymphoid malignancy will succumb to recurrent disease within a short period of time.

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Feasibility and Efficacy of a Planned Second Transplant (“auto” or “mini-allo”) Intensification in Patients with Multiple Myeloma (MM) Not Achieving Complete Remission (CR) or Near-CR with a First Autologous Transplant. Results from a Spanish PETHEMA/GEM Study.

Blood ◽

10.1182/blood.v106.11.425.425 ◽

2005 ◽

Vol 106 (11) ◽

pp. 425-425

Author(s):

L. Rosiñol ◽

J. J. Lahuerta ◽

A. Sureda ◽

J. de la Rubia ◽

J. García-Laraña ◽

...

Keyword(s):

Progressive Disease ◽

Early Death ◽

High Dose ◽

Autologous Transplant ◽

Transplant Patients ◽

Graded Response ◽

Patient Refusal ◽

Cell Support ◽

Reduced Intensity

Abstract It has been shown in non-randomized studies that tandem transplant results in an increased CR rate. A randomized trial showed that tandem transplant resulted in a significantly longer EFS and OS in patients failing to achieve CR or near-CR with a single transplant. However, other studies failed to show a survival benefit from a second transplant. The aim of our study was to investigate the feasibility and efficacy in terms of response up-grading and survival from a second transplant intensification in patients with chemosensitive disease who failed to achieve CR or near-CR with a first transplant. Patients diagnosed with MM from Oct 1999 to Dec 2003 younger than 70 years received 6 courses of VBMCP/VBAD chemotherapy and responding patients were intensified with busulphan/melphalan or MEL-200 followed by stem cell support. Patients not achieving CR or near-CR were planned to undergo a second transplant (either a second auto with CVB - cyclophosphamide, etoposide and BCNU - intensification or a dose-reduced intensity “allo” with Fludarabine/MEL-140 conditioning, depending on sibling donor availability). It is of note that 99 (55%) did not receive the second HDT procedure because patient refusal -28 pts-, lack of CD34–17 pts-, progressive disease - 16 pts-, poor PS -15 pts-, physician decision -14 pts-, others -8 pts-. Patients who did not proceed with the second transplant were significantly older (58 vs. 55 yrs, p= 0.001) and had higher serum beta2-microglobulin levels (4.7 vs. 3.5, p=0.02). Fifty nine patients received a second autologous transplant while 23 underwent a “mini-allo”. Twenty-eight percent of the patients given a second autologous transplant achieved an up-graded response (CR or near-CR: 7%, PR: 10% and MR 12%) while 61% showed “no change”, progressive disease or early death. A response up-grade was observed in 43% of patients undergoing a “mini-allo” procedure (CR: 26%, PR: 4%, MR: 3%). The CR rate was significantly higher with the allogeneic procedure (26 vs. 5%, p=0.01). However, there was a trend towards a higher TRM with the “miniallo” procedure (5% vs. 17% (p=0.09). The survival from the second high-dose procedure was not significantly different between the two transplant modalities (2nd auto vs “mini-allo”). Conclusions. in about one-half of the patients in whom a tandem transplant is planned the second high-dose procedure is not performed, a dose-reduced intensity allogeneic transplant after an autologous procedure results in a significantly higher CR rate than a tandem autologous transplant, with the current follow-up we found no significant differences in survival between the two transplant modalities.

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Tandem Autologous Transplant Versus Reduced Intensity Conditioned Allogeneic Transplant (Allo-RIC) as Second Intensification in Chemosensitive Patients with Multiple Myeloma (MM) Not Achieving Complete Remission (CR) or Near-CR with a First Autologous Transplant. Results from a Spanish PETHEMA/GEM Study.

Blood ◽

10.1182/blood.v110.11.729.729 ◽

2007 ◽

Vol 110 (11) ◽

pp. 729-729

Author(s):

Joan Blade ◽

Laura Rosinol ◽

Juan Jose Lahuerta ◽

Anna Sureda ◽

Javier de la Rubia ◽

...

Keyword(s):

Progressive Disease ◽

Early Death ◽

High Dose ◽

Allogeneic Transplant ◽

Stem Cell Support ◽

Autologous Transplant ◽

Response Status ◽

Second Procedure ◽

Cell Support ◽

Reduced Intensity

Abstract One randomized trial showed that tandem transplant resulted in a significantly longer EFS and OS in patients failing to achieve CR or near-CR with a single transplant. However, other studies failed to show benefit from a second transplant. The aim of our study was to investigate the efficacy in terms of response improvement and survival from a second transplant intensification in patients with chemosensitive disease who failed to achieve CR or near-CR with a first high-dose procedure. Patients diagnosed with MM from Oct 1999 to Dec 2004 younger than 70 years received 6 courses of VBMCP/VBAD and responding patients were intensified with busulphan/melphalan or MEL-200 followed by stem cell support. Patients not achieving CR or near-CR were planned to undergo a second transplant (second auto with CVB - cyclophosphamide, etoposide and BCNU - or MEL-200 intensification or an allo-RIC with Fludarabine/MEL-140 conditioning, if sibling donor available). Eighty-eight patients received a second autologous transplant while 26 underwent an allo-RIC. Thirty-seven percent of the patients given a second autologous transplant improved their response status (CR 11%, near-CR: 6%, PR: 9% and MR 11%) while 63% showed “no change”, progressive disease or early death. A response was observed in 45% of patients undergoing the allo-RIC (CR: 33%, PR: 4%, MR: 8%). The CR rate was significantly higher with allo-RIC (33% vs. 11%, p= 0.02). There was a trend towards a higher TRM with the allo-RIC (5% vs. 16%, p=0.09). Although the median EFS (26 vs 19 m) and OS (57 m vs not reached in allo-RIC) from the second high-dose procedure were not significantly different, there is a plateau in the “allo-RIC” group beyond 3 years of the second procedure not observed in the autologous arm. Conclusions: an allo-RIC transplant after an autologous procedure results in a significantly higher CR rate than a second autologous transplant, and despite the lack of significant differences in survival between the two transplant modalities, there is a plateau in the allogeneic group not observed in the autologous arm.

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PF745 HIGH-DOSE THERAPY AND AUTOLOGOUS TRANSPLANT FOR POEMS SYNDROME: EFFECTIVE, BUT HOW TO OPTIMISE?

HemaSphere ◽

10.1097/01.hs9.0000561264.34965.be ◽

2019 ◽

Vol 3 (S1) ◽

pp. 326-327

Author(s):

O. Tomkins ◽

S. Keddie ◽

A. Cerner ◽

J. Horder ◽

F. Newrick ◽

...

Keyword(s):

Poems Syndrome ◽

High Dose ◽

High Dose Therapy ◽

Dose Therapy ◽

Autologous Transplant

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Progressive disease after high-dose therapy and autologous transplantation for lymphoid malignancy: clinical course and patient follow-up

Blood ◽

10.1182/blood.v80.8.2142.bloodjournal8082142 ◽

1992 ◽

Vol 80 (8) ◽

pp. 2142-2148

Author(s):

JM Vose ◽

PJ Bierman ◽

JR Anderson ◽

A Kessinger ◽

J Pierson ◽

...

Keyword(s):

Bone Marrow ◽

Median Survival ◽

Progressive Disease ◽

High Dose ◽

Lymphoid Malignancy ◽

High Dose Therapy ◽

Durable Response ◽

Dose Therapy ◽

Autologous Transplant ◽

Short Period

Of 364 patients with lymphoid malignancy who underwent high-dose therapy with autologous bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PSCT), 169 patients have had progressive disease after the procedure. The median survival from the time of relapse for patients with Hodgkin's disease (HD) who progressed after the transplant was 10.5 months. This compares with a median survival of 3 months for relapsed non-Hodgkin's lymphoma (NHL) patients (P = .0036). After failing transplantation, 56 patients were treated with further chemotherapy, 35 with involved field irradiation therapy, and 18 patients were treated with combination chemotherapy and irradiation. Seven patients received biologic therapy and seven patients underwent a second bone marrow transplant. The remainder of the patients were believed to be too ill for further therapy or chose not to receive further treatment for their recurrent lymphoid malignancy. Sixty of the 169 patients with progressive disease after the transplant are still alive; however, only 18 patients are alive off therapy without evidence of active disease after their relapse. Ten of the 18 patients are still less than 12 months past their posttransplant salvage therapy and are at high-risk for relapse. Five patients are progression free at 15 to 36 months after their posttransplant relapse. Only three patients (two NHL and one HD) treated with other modalities after autologous transplant failure are alive without evidence of disease and have been observed at least 4 years postrelapse. Although a few patients will have a durable response to subsequent therapy, the majority of patients who have progressive disease after an autologous transplant for lymphoid malignancy will succumb to recurrent disease within a short period of time.

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Pachymeningeal involvement in POEMS syndrome: MRI and histopathological study

Yearbook of Neurology and Neurosurgery ◽

10.1016/j.yneu.2012.04.053 ◽

2012 ◽

Vol 2012 ◽

pp. 49-50

Author(s):

R. Schwendimann

Keyword(s):

Poems Syndrome ◽

Histopathological Study

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