First-line escalated BEACOPP does not hinder stem cell collection and transplantation strategy in patients with relapsed/refractory Hodgkin’s lymphoma

Abstract INTRODUCTION: Traditional platinum-based salvage regimens like DHAP, ICE are effective in relapsed Hodgkin's lymphoma (HL), but are more toxic. Gemcitabine based regimens are equally effective in salvage of lymphomas, but are less toxic and allow better stem cell collection for subsequent high dose therapy (HDT). There is limited data on the usefulness of gemcitabine based salvage regimens after the failure of salvage therapies like DHAP and ICE. At our center, we used a combination of gemcitabine, vinorelbine and dexamethasone (GVDexa), a non-platinum containing regimen in those patients who failed DHAP/ ICE based salvage treatment. METHODS: The records of patients with relapsed and refractory Hodgkin's lymphoma, who were treated with GVDexa, were reviewed. The regimen consisted of Gemcitabine 1000mg/m2 IV (D1,8), Vinorelbine 25mg/m2 IV (D1,8) Dexamethasone 40mg oral (D1-4) given as outpatient. It was given for 2-3 cycles until best response or till the patient underwent HDT. RESULTS: Between July 2010 to Jun 2015, 25 patients received GVDexa. The median age was 23 years (Range: 11 to 45 yrs) and 64% were males. Baseline characteristics are summarised in Table 1. Twenty-one patients (84%) had previous exposure to salvage therapy with DHAP/ ICE and GVDexa was given as third line treatment. The overall response rate was 48% (12/25) with complete response in 20% (5/25) and partial response in 28% (7/25). Toxicity: A total of 61 cycles [Median: 2 (Range: 1-6)] were delivered among 25 patients. Grade 3/4 haematological toxicities (neutropenia and thrombocytopenia) occurred in 9/61 (14.7%) cycles and febrile neutropenia occurred in 2 (3.2%) cycles. Grade 3/4 non-haematological toxicities were rare (paralytic ileus in 1 patient). There were no toxic deaths. Stem cell collection: Stem cell harvesting for HDT was attempted in 12 patients and was successful (> 2 million CD34 positive cells/kg) in 8 (67%) patients. Seven of these patients successfully completed HDT. Two patients who failed stem cell collection underwent reduced intensity conditioning allogeneic transplant. CONCLUSIONS: GVDexa, when used as third line therapy in relapsed and refractory HL shows promising response rates, with minimal toxicity. The high response rates achieved despite failure of first line platinum based salvage, points to the potential usefulness of this regimen as first line salvage therapy in refractory HL. GVDexa could emerge as a safe and effective non-platinum containing alternative regimen for second-line therapy in HL. Table 1. Baseline characteristics (N=25) PARAMETER Number (Range/Percentage) Age (median, range) 23 yrs (10 to 45 yrs) Male sex 16 (64%) Prior exposure to DHAP/ICE chemotherapy 21 (84%) Previous lines of chemotherapy (median, range) 2 (1 to 4) Time from 1st diagnosis to relapse (median, range) 31.5 months (4.3 to 153.7 months) Primary progressivea/refractory 13 (52) Stage III/IV at relapse 20 (80) Haemoglobin < 10g/dL at relapse 12 (48) a. Progressed within 3 months of completion of first line chemotherapy Disclosures No relevant conflicts of interest to declare.

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Timing of G-CSF Injection for Effective Autologous Stem Cell Collection

Blood ◽

10.1182/blood.v112.11.4439.4439 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4439-4439

Author(s):

Jeong-Eun Kim ◽

Cheolwon Suh ◽

Yunsuk Choi ◽

Eun Kyoung Kim ◽

Byeong Seok Sohn ◽

...

Keyword(s):

Stem Cell ◽

Hodgkin’S Lymphoma ◽

Median Number ◽

Hodgkin's Lymphoma ◽

Peripheral Blood Stem Cells ◽

Patients Âgés ◽

Peripheral Stem Cell ◽

Number Of Patients ◽

Cd34 Cells ◽

Stem Cell Collection

Abstract Granulocyte colony-stimulating factor (G-CSF) has been given approximately 12 hours before leukapheresis in the patients who are planned to do autologous stem cell collection. The objective of this study was to identify better timing of G-CSF administration which improves the efficacy of autologous stem cell collection. A total of 262 patients (157 male and 105 female patients, ages from 15 to 66 years with median of 49 years) who underwent autologous stem cell collection from January 2000 to March 2008 were included. The patients were diagnosed with Hodgkin’s lymphoma (N=19), non-Hodgkin’s lymphoma (N=131) and multiple myeloma (N=112). Peripheral blood stem cells were mobilized with lenograstim (Choongwae Pharma Corp., Seoul, Korea) following chemotherapy, such as cyclophosphamide (N=141), ESHAP (Etoposide, methylprednisolone, Ara-C and cisplatin, N=73) with (N=14) or without rituximab (N=59) and other chemotherapy regimens (N=48). Before November 2004, patients received lenograstim injection at a dose of 10 μg/kg subcutaneously at 8:00 PM and underwent peripheral stem cell collection on next day (N=129). After then patients received lenograstim injection at 6:00 AM and underwent peripheral stem cell collection at the same day (N=133). Injection of lenograstim at 6 AM was superior to injection of lenograstim at 8 PM with greater numbers of total collected CD34+ cells/kg in shorter duration of leukapheresis procedures (13.29 × 106 versus 8.51 × 106 CD34+ cells/kg; p=0.001, 2 versus 3 leukapheresis procedures; p=0.035). The median number of CD34+ cells/kg collected at first leukapheresis was also greater in 6 AM group (3.94 × 106 versus 2.47 × 106 CD34+ cells/kg; p=0.001). Stem cell collection efficacy defined as ratio of total collected CD34+ cells per days of leukpaheresis were 5.34 and 2.96, respectively. It was significantly better in the group of patients received lenograstim injection at 6 AM (p=0.001). The median number of patients who achieved a total collected CD34+ cells > 5 × 106/kg was also greater in 6 AM group (113 versus 96; p=0.002). The present study shows that injection of lenograstim at 6 AM improves the efficacy of stem cell collection with greater number of collected CD34+ cells/kg in shorter duration of leukapheresis procedures compared to that of 8 PM group.

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Time Interval from Last Chemotherapy to Stem Cell Collection Correlates with Peripheral Blood Absolute Lymphocyte Count at Apheresis and Survival Post-Autologous Stem Cell Transplantation in Non-Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v104.11.2927.2927 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2927-2927 ◽

Cited By ~ 1

Author(s):

Shernan G. Holtan ◽

Luis F. Porrata ◽

David J. Inwards ◽

Stephen A. Ansell ◽

Ivana N.M. Micallef ◽

...

Keyword(s):

Stem Cell ◽

Peripheral Blood ◽

Lymphocyte Count ◽

Hodgkin’S Lymphoma ◽

Group Versus ◽

Absolute Lymphocyte Count ◽

Hodgkin's Lymphoma ◽

Time Interval ◽

Non Hodgkin's Lymphoma ◽

Stem Cell Collection

Abstract The infused autograft absolute lymphocyte count (A-ALC) is an independent prognostic factor for survival after autologous hematopoietic stem cell transplant (AHSCT) in non-Hodgkin’s lymphoma (NHL). Previous studies have shown that A-ALC directly correlates with the peripheral blood absolute lymphocyte count (PC-ALC) at the time of apheresis collection. However, factors affecting the PC-ALC at apheresis remain undefined. We hypothesized that one possible factor impacting PC-ALC may be the time interval from last chemotherapy to stem cell collection (TILC). Data from 160 patients who underwent AHSCT for treatment of relapsed NHL at Mayo Clinic between 1993 and 2001 were collected and analyzed. The primary end point of this study was correlation between TILC and PC-ALC, and our analysis revealed a strong correlation (r = 0.67, p < 0.0001). Further analysis revealed higher PC-ALC numbers in patients with TILC ≥ 60 days versus TILC < 60 days (median of 7.44 x 109/L in the ≥ 60 day group versus 3.87 x 109/L in the < 60 day group, p < 0.0001). Both the median overall survival (figure below) and the progression-free survival were longer in the TILC ≥ 60 days group versus the TILC < 60 days group (76 versus 21 months, p < 0.0037; 76 versus 11 months, p < 0.018, respectively). These findings were independent of other prognostic indicators for relapsed NHL patients undergoing APHSCT. The data supports our hypothesis that TILC affects PC-ALC and survival post-AHSCT in NHL. Figure Figure

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ROLE OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN CHILDREN WITH HODGKIN’S LYMPHOMA

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2020-99-4-42-50 ◽

2020 ◽

Vol 99 (4) ◽

pp. 42-50

Author(s):

A.V. Kozlov ◽

◽

T.V. Yukhta ◽

P.S. Tolkunova ◽

A.G. Gevorgyan ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Hodgkin’S Lymphoma ◽

Hodgkin's Lymphoma ◽

Hematopoietic Stem

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A Study to Evaluate the Efficacy and Safety of the Sintilimab Plus ICE Regimen Versus ICE Regimen in the Classic Hodgkin's Lymphoma Patients (cHL) Who Have Failed the First-line Standard Chemotherapy

Case Medical Research ◽

10.31525/ct1-nct04044222 ◽

2019 ◽

Author(s):

Keyword(s):

Hodgkin’S Lymphoma ◽

Hodgkin's Lymphoma ◽

Efficacy And Safety ◽

First Line ◽

Standard Chemotherapy ◽

Line Standard

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Prognostic and predictive factors in early stages of classic Hodgkin’s lymphoma

Medical alphabet ◽

10.33667/2078-5631-2021-37-7-15 ◽

2022 ◽

pp. 7-15

Author(s):

T. I. Bogatyreva ◽

A. O. Afanasov ◽

A. Yu. Terekhova ◽

N. A. Falaleeva

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Hodgkin’S Lymphoma ◽

Early Stage ◽

Hodgkin's Lymphoma ◽

Cure Rate ◽

First Line ◽

Bulky Disease ◽

Cox Regression Analysis ◽

Early Stages

Rationale. In the early stages of classical Hodgkin’s lymphoma (cHL), the cure rate reaches 85–95 %, but the long-term effects of therapy can worsen overall survival. Current trials for early stages of Hodgkin’s lymphoma with favorable prognosis address the task of maintaining cure rates while reducing sequelae. For early unfavorable stages, the challenge is to improve cure rate without increasing toxicity.Purpose. To assess the potential significance of individual risk factors for optimal choice of the first line chemotherapy in early-stage Hodgkin lymphoma.Materials and methods. This single-center retrospective study included 290 patients with early stage cHL who had received ABVD – based (n = 249; 86 %) or BEACOPP‑21 – based (n = 41; 14 %) combined modality therapy from 2000 to 2017. Progression-free survival (PFS) and overall survival (OS) were assessed in Cox regression analysis including 12 clinical parameters.Main results. At a median follow up of 60 months for the entire group, OS was 95 % and PFS was 89 %. In a multivariate analysis PFS, at 5 years, was significantly inferior in patients with mediastinal bulk, baseline lymphocytopenia (≤ 0.6 × 109/L, р = 0.002; < 1.0 × 109/L, р = 0.000) and male gender; OS was inferior only in patients with an absolute lymphocytopenia (AL). In patients with AL, PFS after ABVD-based regimen was, respectively, 12 % in the high-risk group with mediastinal bulk and 56 % without it. PFS of patients without AL when treated with ABVD did not differ compared to BEACOPP‑21 within the same prognostic group: 95.2 % vs. 92.3 % for non-bulky and 86.4 % vs. 84.2 % for bulky disease. In the absence of AL, mediastinal bulk remained the main and only risk factor in multivariate analysis.Conclusions. The ABVD regimen is highly effective in the first line of chemotherapy for cHL, except for cases with baseline lymphocytopenia, in which the early usage of the BEACOPP regimen in the escalated or 14-day variants might be justified. In patients with mediastinal bulk, standard chemotherapy is not effective enough even in the absence of AL; therefore, if an intermediate PET/CT scan is available, it seems more appropriate to use a milder ABVD regimen on the first line and leave intensive therapy for patients with proven refractory disease. Prospects for improving the efficiency are opened with the new N-AVD and A-AVD schemes, the benefits of which should be evaluated, first of all, in patients with AL and mediastinal bulk.

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