Effective mobilization with etoposide and cyclophosphamide for collection of peripheral blood stem cell in patients with multiple myeloma

Purpose: To evaluate the efficacy and toxicity of etoposide and cyclophosphamide for mobilization peripheral stem cells in multiple myeloma patients. Methods: We retrospectively analyzed 46 patients with multiple myeloma who underwent peripheral blood stem cell collection for upfront autologous hematopoietic stem cell transplantation in the First Affiliated Hospital of Xi’an Jiaotong University between January 2010 and July 2019. The mobilization protocols included cyclophosphamide 2.0 g/m2 with G-CSF (CTX group) before January 2015, and two-days of 5 mg/kg.d etoposide and 1.0 g/m2.d cyclophosphamide with G-CSF (EC group) after January 2015. Results: The success rate of harvest (≥2×106 cells/kg) during the first mobilization attempt was 82.1% in the EC group and 50.0% in the CTX group, and the rate of adequate harvest (≥4×106 cells/kg) was 57.1% in the EC group and 15.8% in the CTX group. After the second mobilization, a sufficient number of CD34+/kg cells for an auto-HSCT was obtained for all patients in the EC group and the majority (68.4%) of patients in CTX group. There was no significant difference of non-hematological adverse events between two groups. The mean neutrophil engraftment time was 11.22±1.56 days and 9.89±2.81days for the CTX and EC groups, respectively (P>0.05). Platelet engraftments were significantly faster in the EC group than the CTX group (P0.05). Conclusion: The etoposide and cyclophosphamide regimen could be an effective and safe method for mobilization in patients with multiple myeloma.

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Modified Thalidomide, Cyclophosphamide and Dexamethasone (TCD) to Patients with Multiple Myeloma as Primary Therapy Prior to Peripheral Blood Stem Cell Collection.

Blood ◽

10.1182/blood.v106.11.5173.5173 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5173-5173

Author(s):

Deok-Hwan Yang ◽

Je-Jung Lee ◽

Yeo-Kyeoung Kim ◽

Jin-Ho Baek ◽

Sang-Kyun Sohn ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Peripheral Blood ◽

Peripheral Blood Stem Cell ◽

Complete Response ◽

Blood Stem Cell ◽

High Dose ◽

Primary Therapy ◽

Hematopoietic Stem ◽

Stem Cell Collection

Abstract In the treatment of multiple myeloma (MM), autologous peripheral blood stem cell (PBSC)-supported high-dose melphalan is now considered standard therapy, especially for younger patients. Before PBSC, a new immunomodulatory drug, thalidomide, has replaced VAD regimen as the induction therapy of choice prior to hematopoietic stem cell procurement. Thalidomide has alternative mechanisms of action and usually combines with dexamethasone or alkylating agent, but the optimal doses and the intervals of chemotherapy has been evaluated. We reported preliminary data that the patients with previously untreated multiple myeloma were treated by combined different dose-scheduled thalidomide, cyclophosphamide, and dexamethasone as primary therapy and performed autologous stem cell collection. A total of 52 patients with MM were initially treated thalidomide-based chemotherapy from June 2003. Thalidomide was given with the three different method: 400mg/day on D1–5, D15–19 (arm A), 50mg/day daily (arm B) combined with cyclophosphamide 150mg/m2 P.O. on D1–4 and dexamethasone 20mg/m2 P.O. or I.V. on D1–5, D15–19, or thalidomide 200mg/day daily combined with dexamethasone 20mg/m2 on D1–4, 9–12, 17–20 in odd cycles and on D1–4 in even cycles (arm C), repeated every 28 days. Low-dose aspirin or warfarin was taken as prophylaxis for thrombosis. Thirty-nine (arm A: 17, arm B: 12, arm C: 10) of the 52 patients who received at least 4 cycles or more were evaluated for response and toxicity. Median age was 65 (range: 39–80) years and the total number of 158 cycles of toxicities were evaluated. After median 4 months of time to response followed, the overall response rate was 71.8% (76.5% v 75.0% v 60.0%), including 23% (17.5% v 23% v 28%) of complete or near complete response. Two patients (5.1%) died due to infection during treatment. When the toxicity of therapy was evaluated with more Grade III, two patients (5.1%) showed neurotoxicity, six patients (15.4%) showed neutropenia, and two patients (5.1%) had deep-vein thrombosis. Thirteen patients who achieved more than partial response proceeded to PBSC collection and yielded a median number of 3.78 x 106 CD 34+ cells/kg. This low or intermediate dose or periodic thalidomide combination showed positive responses, reducing toxicities, and adequate numbers of blood stem cells in patients eligible for subsequent high-dose chemotherapy.

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Advanced lytic lesion is a poor mobilization factor in peripheral blood stem cell collection in patients with multiple myeloma

Journal of Clinical Apheresis ◽

10.1002/jca.21326 ◽

2014 ◽

Vol 29 (6) ◽

pp. 305-310 ◽

Cited By ~ 2

Author(s):

Sung-Hoon Jung ◽

Deok-Hwan Yang ◽

Jae-Sook Ahn ◽

Yeo-Kyeoung Kim ◽

Hyeoung-Joon Kim ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Peripheral Blood ◽

Peripheral Blood Stem Cell ◽

Blood Stem Cell ◽

Lytic Lesion ◽

Stem Cell Collection

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Bortezomib Plus Dexamethasone As Induction Treatment Followed by Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma: A Study From India

Blood ◽

10.1182/blood.v118.21.4584.4584 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4584-4584 ◽

Cited By ~ 1

Author(s):

Shyam Aggarwal ◽

Anshul Bhalla ◽

S.L Khatri ◽

Anand Simar S ◽

Manorama Bhargava ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Peripheral Blood ◽

Progressive Disease ◽

Peripheral Blood Stem Cell ◽

Blood Stem Cell ◽

Induction Regimen ◽

Stem Cell Collection ◽

Blood Stem Cell Transplantation

Abstract Abstract 4584 Background and Objectives – Multiple myeloma (MM) is an incurable hematological malignancy, afflicting 25000 patients each year in India. Complete remission in myeloma is a surrogate marker for improved survival. The objective of induction regimen, using novel agents such a bortezomib, and Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) is to increase the number of patients achieving CR. Here, we report a retrospective evaluation of the efficacy and response rates of induction with Bortezomib (Velcade) plus Dexamethasone (VD Regimen) followed by APBSCT and its effect on stem cell collection and final outcome of the transplant. Methods – Ten patients with symptomatic MM who had received VD induction before stem cell collection were evaluated. VD Induction comprised of Bortezomib (1.3 mg/m2) and Dexamethasone (40 mg) administered on days 1, 4, 8, 11 for four 21-day cycles. Peripheral blood stem cell collection technique involved administration of granulocyte stimulating factor (G-CSF); 300 mg/kg administered twice daily for 5 days. Adequate number of stem cells was collected in nine patients by a single harvest. One patient required apharesis twice for adequate stem cell collection. These cells were cryo-preserved. High dose Melphalan (200 mg/m2) was given followed by stem cell transfusion. Results – The median CD34-positive stem cell count was 5.6 × 106/kg. All the patients engrafted post transplant. The median time for engraftment i.e. Absolute Neutrophil Count (ANC) > 500/mL was 10 days and Platelet Count > 50000/mL was 16 days. The median length of hospital stay was 21 days. They were successfully managed for fever and infections with antibiotics, antifungals and supportive treatment. Irradiated blood (median - 4 units) and platelet apharesis (median – 3 units) were given. Response was assessed according to International Myeloma Working Group uniform response criteria. After induction with VD protocol, the overall response rate (ORR) was 90%. 2 patients (20%) had a complete response (CR), 7 patients (70%) had very good partial response (VGPR) and 1 patient (10%) had progressive disease. Post – APBSCT, the patient with progressive disease achieved VGPR and 6 out of 7 patients (85.7%) with VGPR achieved CR making the total responses as 8 CRs and 2 VGPRs. Thus, ORR was 100%, including 80% CR rate and 20% VGPR rate. All patients were put on maintenance therapy, 6 patients were on thalidomide (50 mg/day) and 4 patients received lenalidomide (10 mg/day) therapy. In the analysis, the median progression-free survival (PFS) was not reached at 22 months. The median overall survival (OS) was not reached after a median follow-up of 25 months, and the 2-year OS rate was 70%. Three patients (30%) had a relapse post-APBSCT, after 5 months, 9 months and 18 months respectively. Two patients (20%) expired, one due to myeloma and the other due to unrelated cause. All three patients with renal insufficiency experienced improvement in renal function and did not require dialysis post-APBSCT. Two patients (20%) developed neuropathy and two patients (20%) developed Herpes Zoster infection due to bortezomib therapy. Conclusions – The induction regimen of bortezomib plus dexamethasone is effective and well tolerated in symptomatic myeloma patients. It significantly improves post-induction and post-transplantation CR and VGPR rates and does not affect stem cell mobilization and collection procedure. Disclosures: No relevant conflicts of interest to declare.

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Retrospective analysis of an efficient peripheral blood stem cell collection and the relation between infused cell dose and clinical outcome in patients with malignant lymphoma and multiple myeloma

International Journal of Laboratory Hematology ◽

10.1111/j.1751-553x.2012.01410.x ◽

2012 ◽

Vol 34 (4) ◽

pp. 403-409

Author(s):

Y. TSUTSUMI ◽

R. OGASAWARA ◽

S. ITO ◽

J. SASAKI ◽

A. MORITA ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Clinical Outcome ◽

Malignant Lymphoma ◽

Retrospective Analysis ◽

Peripheral Blood ◽

Peripheral Blood Stem Cell ◽

Blood Stem Cell ◽

Cell Dose ◽

Stem Cell Collection

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No Influence of Previous Thalidomide Administration on Peripheral Blood Stem Cell Collection in Patients with Multiple Myeloma.

Blood ◽

10.1182/blood.v104.11.4902.4902 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4902-4902

Author(s):

Iris Breitkreutz ◽

Axel Benner ◽

Friedrich W. Cremer ◽

Doris Herrmann ◽

Anthony D. Ho ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Total Dose ◽

Induction Therapy ◽

Peripheral Blood ◽

Peripheral Blood Stem Cell ◽

Blood Stem Cell ◽

Cd34 Cells ◽

To Receive ◽

Stem Cell Collection

Abstract OBJECTIVES: In a joint study of the GMMG and HOVON groups, induction therapy with Thalidomide (Thal), doxorubicin and dexamethasone (TAD) is currently investigated in comparison with vincristin, doxorubicin and dexamethasone (VAD) followed by mobilisation therapy with cyclophosphamide, doxorubicin and dexamethasone (CAD) and peripheral blood stem cell collection (PBSC). Munshi et al. (Blood 1999, Abstract #2577) described a dampening of PBSC-mobilisation by Thal treatment. We therefore investigated a possible influence of PBSC after previous Thal administration. METHODS: Altogether, data on 112 patients were analyzed in terms of PBSC-mobilisation. 56 patients were randomized up-front to receive 3 cycles of TAD (Thal 400mg/d orally; doxorubicin 9mg/m2/d, 4 30-min. infusions, day 1–4; dexamethasone 480mg total dose orally). 56 patients received VAD (vincristin 0,4mg/d and doxorubicin 9mg/m2/d, 4 30-min. infusions, day 1–4.; dexamethasone 480mg total dose orally) followed by mobilisation with CAD (cyclophosphamide 1g/m2/d, 1h infusion, day 1; doxorubicin 15mg/m2/d, 4 short infusions, day 1–4; dexamethasone 160mg total dose orally) and G-CSF (Neupogen 600mg/d s.c. or Granocyte 526mg/d s.c., day 5 after the end of chemotherapy until PBSC). Thal was stopped two weeks before CAD. Low dose heparine was administered to prevent deep venous thromboses in the TAD group. RESULTS: The median time was 14 days after the first day of CAD until PBSC in patients in both the TAD (range 12–18 days) and VAD group (range 10–19 days). In the first leukapheresis, a median total PBSC yield of 8,1x106/kg CD34+ cells in the TAD/CAD (range 0,3–34x106 CD34+ cells) and 8,7x106/kg CD34+ cells in the VAD/CAD (range 0,5–30x106 CD34+ cells) group could be harvested (p=0.31). In the best leukapheresis, a median total PBSC yield of 8,1x106/kg CD34+ cells in the TAD/CAD (range 0,7–34x106 CD34+ cells) and 8,9x106/kg CD34+ cells in the VAD/CAD (range 2–30x106 CD34+ cells) group could be reached (p=0.24). CONCLUSIONS: No difference was found in stem cell collection and yield after TAD versus VAD. Thalidomide as a part of induction therapy does not seem to have an influence of the peripheral blood stem cell collection of patients with multiple myeloma.

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Faculty Opinions recommendation of Thalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral blood stem cell collection yield.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1083814.536744 ◽

2007 ◽

Author(s):

Michele Cavo

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Peripheral Blood ◽

Peripheral Blood Stem Cell ◽

Blood Stem Cell ◽

Newly Diagnosed ◽

Thalidomide Treatment ◽

Stem Cell Collection

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A Report of Fourcases of Severethrombocytopenia with Rh G-CSF Mobilized Allogeneic Peripheral Blood Stem Cell Transplant Donors

Blood ◽

10.1182/blood-2020-141209 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 22-22

Author(s):

Qingzhen Liu ◽

Jianfeng Yao ◽

Donglin Yang ◽

Aiming Pang ◽

Erlie Jiang ◽

...

Keyword(s):

Stem Cell ◽

Peripheral Blood ◽

Healthy Donor ◽

Peripheral Blood Stem Cell ◽

Blood Stem Cell ◽

Severe Thrombocytopenia ◽

Hematopoietic Stem ◽

Healthy Donors ◽

Stem Cell Collection

Background and Objective: Granulocyte colony-stimulating factor (G-CSF) is used to mobilize progenitor cells into the peripheral bloodin healthy donors. Thrombocytopenia is one of common side effects of G-CSFmobilization, but seriousthrombocytopenia is rare. Herein,we report serious thrombocytopeniain 4 allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) healthy donors induced by recombinant human G-CSF (rhG-CSF) mobilization. Methods: The donor received 10ug/kg/d G-CSF via subcutaneous injection.The blood parameterswere examined every day, Abdominal ultrasound detected the spleen size before, during, and after rhG-CSF mobilization. Results: From April 2015 to May 2020, 1127 donors received hematopoietic stem cell mobilization, the percentage of serious thrombocytopenia in healthy donors was 0.35%.The count of white blood cell increased to the 4-7 timesbasic level of (35.4x109/L)after rhG-CSF mobilization 4 days, the lowestcount ofplatelet was 22x109/Lafter single postharvest. After mobilization, length of spleen increased 0.6-1.3 cm (median 10.1 cm), thickness ofspleenincreased 0-1.3 cm (median 3.4 cm). There were no obvious bleeding symptomsafter mobilization in four cases of donor.The quality of stem cell collection was relatively poor in 3 of the 4 donors, the number of mononuclear cells (MNC) was 7.47-18.58×108/kg, and the value of CD34+ was 0.82-2.42×106/kg (CD34+ proportion: 0.11-0.16%). The quality of stem cell collection in the other 1 donor was satisfactory, the number of MNC was 9.29-11.75×108/kg, and the proportion of CD34+ was 0.26~0.38%. Platelet count of 4 donors recovered to the basal level 3-10 days after drug withdrawal. Conclusion:The severe thrombocytopenia caused by rhG-CSF mobilization healthy donor is very rare.while, the mechanismis unknown. Some studies suggested that it may be related to the insufficient expression of megakaryocytes proliferation-related genes, such as PF4 and PTFN4. Other studies indicated that rhG-CSF may aggravate the immune-mediated thrombocytopenia, which leads to hypersplenism and extensive activation of reticuloendothelial cells, thus increasing the consumption of platelets.In addition, the probability of severe thrombocytopenia was increased in allergic donors after rhG-CSF mobilization.In our report, although there was thrombocytopenia, mobilization was not affected.After the mobilization of rhG-CSF, platelets changes should be closely monitored to keep alert of donor bleeding tendency. While ensuring safe collection of hematopoietic stem cells by donors, patients should not be placed in extreme danger of not being able to receive allogeneic hematopoietic stem cells on time. Key words:Severe thrombocytopenia;Healthy donor; rhG-CSF; Mobilization; Allogeneic peripheral blood stem cell transplantation. Disclosures No relevant conflicts of interest to declare.

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