Very High Efficacy of Bendamustine, Gemcytabine and Dexamethasone (BGD) in Relapsed/Refractory Classical Hodgkin Lymphoma

Abstract Introduction. Although Hodgkin lymphoma (HL) is one of the most curable malignancies, 10-30% of patients experience resistance or relapse following initial response. Treatment options for relapsed/refractory (R/R) disease include usually multi-agent chemotherapy followed by autologous hematopoietic stem cell transplantation (autoHSCT). Although many chemotherapy-based regimens are used as salvage, the optimal one has not been defined so far. The goal of this study was to evaluate efficacy and safety of bendamustine in combination with gemcitabine and dexamethasone (BGD) in R/R HL. Patients and Methods. This was a retrospective, single center study, including 30 consecutive R/R HL patients treated between 2016 and 2018. Median age was 33 (19-82) years. Ten patients (33%) had been pre-treated with at least 2 lines of chemotherapy; 11 patients (37%) with radiotherapy, 6 patients (20%) with autoHSCT while 4 patients (13%) with allogeneic (allo)HSCT. Six patients (20%) were resistant to previous salvage treatment. BGD therapy consisted of bendamustine 90mg/m2 on days 1 and 2, gemcitabine 800 mg/m2 on days 1 and 4, dexamethasone 40 mg on days 1-4. Best response after at least 2 courses of therapy was the primary study end-point. Results. Median number of BGD cycles was 4 (2-7). Nineteen (63%) patients achieved complete remission (CR) confirmed by FDG-PET, while 6 patients (20%) achieved partial response (PR), accounting for 83% overall response (OR) rate. Stable disease was reported in 3 patients and progressive disease - in 2 cases. Many patients achieved CR (33%) or PR (33%) after 2 cycles of BGD. The OR rate was 85% for patients in whom BGD was administered as first salvage and 80% when used in more advanced stages of the disease. Fourteen patients proceeded to autoHSCT while 4 patients were subsequently treated with alloHSCT. Six patients experienced infections of the upper respiratory tract while two patients had allergic skin reactions. No organ toxicity was reported. One patient required transfusion of red blood cells while none was treated with platelet transfusions. Conclusion. BGD is a highly effective, well-tolerated salvage regimen for patients with R/R HL. The protocol may be used as a bridge to autoHSCT or alloHSCT. Further, prospective studies are warranted to define its role in future treatment algorithms. Disclosures No relevant conflicts of interest to declare.

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High efficacy of BGD (bendamustine, gemcitabine, and dexamethasone) in relapsed/refractory Hodgkin Lymphoma

Annals of Hematology ◽

10.1007/s00277-021-04448-5 ◽

2021 ◽

Author(s):

Ryszard Swoboda ◽

Sebastian Giebel ◽

Wanda Knopińska-Posłuszny ◽

Ewa Chmielowska ◽

Joanna Drozd-Sokołowska ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Progression Free Survival ◽

Median Number ◽

Efficacy And Safety ◽

First Line ◽

Salvage Regimen ◽

Hematopoietic Stem ◽

Free Survival ◽

Line Of Therapy ◽

Refractory Hodgkin Lymphoma

AbstractThe optimal salvage therapy in relapsed/refractory Hodgkin lymphoma (R/R HL) has not been defined so far. The goal of this multicenter retrospective study was to evaluate efficacy and safety of BGD (bendamustine, gemcitabine, dexamethasone) as a second or subsequent line of therapy in classical R/R HL. We have evaluated 92 consecutive R/R HL patients treated with BGD. Median age was 34.5 (19–82) years. Fifty-eight patients (63%) had received 2 or more lines of chemotherapy, 32 patients (34.8%) radiotherapy, and 21 patients (22.8%) an autologous hematopoietic stem cell transplantation (autoHCT). Forty-four patients (47.8%) were resistant to first line of chemotherapy. BGD therapy consisted of bendamustine 90 mg/m2 on days 1 and 2, gemcitabine 800 mg/m2 on days 1 and 4, dexamethasone 40 mg on days 1–4. Median number of BGD cycles was 4 (2–7). The following adverse events ≥ 3 grade were noted: neutropenia (22.8%), thrombocytopenia (20.7%), anemia (15.2%), infections (10.9%), AST/ALT increase (2.2%), and skin rush (1.1%). After BGD therapy, 51 (55.4%) patients achieved complete remission, 23 (25%)—partial response, 7 (7.6%)—stable disease, and 11 (12%) patients experienced progression disease. AutoHCT was conducted in 42 (45.7%) patients after BGD therapy, and allogeneic HCT (alloHCT) in 16 (17.4%) patients. Median progression-free survival was 21 months. BGD is a highly effective, well-tolerated salvage regimen for patients with R/R HL, providing an excellent bridge to auto- or alloHCT.

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Efficacy of Brentuximab Vedotin and Bendamustine Combination in Relapsed/Refractory Hodgkin Lymphoma: Experience from a Tertiary Care Hospital

Blood ◽

10.1182/blood-2021-152911 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4532-4532

Author(s):

Abdullah M Alrajhi ◽

Razan A. Aljalali ◽

Lara H. Alghazi ◽

Ibrahim Asiri ◽

Adel Alnakhli ◽

...

Keyword(s):

Stem Cell ◽

Hodgkin Lymphoma ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Median Number ◽

Brentuximab Vedotin ◽

Cell Transplant ◽

Salvage Regimen ◽

Hematopoietic Stem ◽

Refractory Hodgkin Lymphoma

Abstract Background: Hodgkin lymphoma (HL) is an uncommon B-cell malignant neoplasm, with high curable rate for patients with localized disease or advanced.However, up to 30% of patients with HL are either refractory or relapsed after primary treatment. Salvage chemotherapy followed by autologous hematopoietic stem cell transplant (HSCT) is the standard of care for eligible patients in relapsed setting. Brentuximab vedotin and Bendamustine (BvB) combination have been recommended by National Cancer Center Network (NCCN) as one of the salvage regimens for patients with relapsed or refractory HL prior to transplant or who relapsed after hematopoietic stem cell transplant (HSCT). Evidence from retrospective and prospective studies in regards of BvB have shown remarkable progression free survival (PFS) with 2-years PFS ranging from 62.2% up to 93.7%, and overall survival (OS) ranging from 88.1% up to 95%, and complete remission (CR) rates ranging from 43% to 90%. The objective of this study is to assess patient response to BvB in the treatment of relapsed/refractory HL especially for patients beyond first salvage therapy unlike many other studies. Methods: A retrospective study was conducted in patients with relapsed/refractory Hodgkin lymphoma treated with BvB chemotherapy at single tertiary hospital from January 2016 until July of 2021. Data collection was done including patient demographics data, comorbidities, disease stage, lines of chemotherapy regimens taken, and PET scan response with Deauville score. Brentuximab was given as 1.8mg/kg on day 1, and bendamustine was given as 90mg/m 2 on day 1 and day 2. Cycle was repeated every three weeks. Result: A total of 16 patients with relapsed/refractory HL whom treated with BvB chemotherapy were analyzed. Median age is 29 years (22-70 years), 5 patients were female, and median number of lines of therapy prior to starting BvB is 2 (0-5). The median number of cycles of BvB was 5.5 (3-8 cycles). 2 out of 16 patients had a prior autologous HSCT (12.5%). 15 patients were assessed for response and one patient died before disease assessment. The overall response rate was 80% with 50% of patients achieving complete metabolic response on PET scan. After median follow up of 14.5 months, the median PFS was 13.4 months (Figure 1), and the median OS was not reached (Figure 2). 4 patients underwent HSCT (3 autologous, and 1 allogeneic). Conclusion: BvB combination is an effective outpatient-based salvage regimen for heavily pretreated patients with multiple lines chemotherapy in relapsed/refractory HL, as majority of patients in our study were beyond first salvage. As there is no standard salvage regimen in this setting, randomized trials are needed to compare efficacy and safety BvB with other established regimens. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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High-Dose Methotrexate, Ifosfamide, Etoposide and Dexamethasone (MIED) Is an Active Salvage Regimen for Children with Recurrent or Refractory Malignant Lymphoma.

Blood ◽

10.1182/blood.v110.11.3434.3434 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3434-3434

Author(s):

John T. Sandlund ◽

Ching-Hon Pui ◽

Yinmei Zhou ◽

Eric J. Lowe ◽

Sue C. Kaste ◽

...

Keyword(s):

Malignant Lymphoma ◽

Hodgkin Lymphoma ◽

Large Cell ◽

High Dose ◽

High Dose Methotrexate ◽

Salvage Regimen ◽

Hematopoietic Stem ◽

Not Otherwise Specified ◽

Dose Methotrexate ◽

Disease Free

Abstract Significant advances have been made in the treatment of malignant lymphomas in children; however, approximately 20–30% will have refractory or recurrent disease. These patients are felt to have a relatively poor prognosis primarily because of the comprehensive and intensive nature of their frontline therapies; therefore, they are generally considered for a novel or more aggressive salvage regimen. The purpose of this study is to determine the activity and toxicity profile of the MIED regimen (high-dose methotrexate, ifosfamide, etoposide and dexamethasone) in children with refractory or recurrent non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). From 1991 to 2006, 62 children with refractory/recurrent NHL (n=24) and HL (n=38) were treated with 1 to 6 sequential cycles of MIED (methotrexate, 8 grams/m2 on day 1; ifosfamide, 2 grams/m2 on days 2–4; etoposide, 200 mg/m2 on days 2–4; and dexamethasone, 40 mg/m2 on days 1–4). Children with NHL also received intrathecal MHA (methotrexate, hydrocortisone, and cytarabine at age adjusted dosages) on day 1. Response evaluation was performed after 1 – 2 cycles of MIED. Children with either a PR or CR were considered for an intensification phase with hematopoietic stem cell transplantation (HSCT); patients with HL also received involved-field irradiation. Forty-six (75%) of the 61 evaluable children with refractory or recurrent lymphoma responded to MIED (CR, 23; PR, 23). Among the 24 children with NHL (large cell, 18 [anaplastic large cell, 8; diffuse large B-cell, 3; T-cell large cell, 2; large cell not otherwise specified, 5]; Burkitt, 3; lymphoblastic, 2; other, 1), responses included: CR (n=10), and PR (n=5) for a combined CR+PR rate of 63%. Among the 37 children with HL (nodular sclerosis, n = 29; mixed cellularity, n =4; lymphocyte predominant, n =1; and HL not otherwise specified, n=3) responses included: CR (n=13), and PR (n=18) for a combined CR+PR rate of 84% among 37 evaluable patients. MIED was generally well tolerated (associated with grade IV hematologic toxicity in most cases and frequently associated with mucositis and/or fever with neutropenia). Nineteen of 24 children with NHL and 31 of 37 children with HL received an intensification phase with HSCT support (autologous, 46; allogeneic, 4) at some point following MIED therapy. Nine of 24 children (38%) with NHL are alive and disease-free. Twenty-eight of 37 children (76%) with HL are currently alive (24 disease-free post HSCT). MIED is an active and generally well tolerated regimen for children with refractory or recurrent malignant lymphoma.

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Chronic Myeloid Leukemia Philadelphia Chromosome Positive (CML Ph+) with Imatinib (IM) Intolerance or Resistant Disease. Response to Thalidomide (TALI) Treatment. Preliminary Report of a Serial of Cases with Encouraging Results

Blood ◽

10.1182/blood.v120.21.1689.1689 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1689-1689

Author(s):

Rafael Hurtado ◽

Jose Pablo Vargas Viveros ◽

Carrillo Muñoz Silvia ◽

Judith Cruz-Velazquez ◽

Myrna Candelaria ◽

...

Keyword(s):

Conflicts Of Interest ◽

Treatment Options ◽

Philadelphia Chromosome ◽

Cytogenetic Response ◽

Nf Kappa B ◽

Hematopoietic Stem ◽

Disease Response ◽

Resistant Disease ◽

First Case ◽

Investigational Agents

Abstract Abstract 1689 The increase dose of Imatinib, the shift to a Tyrosine Kinase (TKI) inhibitor of second generation or hematopoietic stem cell transplantation are treatment options when there is loss or lack of response to IM in CML; However, in patients without access to these therapeutic alternatives, the use of alkylating drugs or investigational agents is indicated. NF Kappa B pathway is constitutively activated in CML patients therefore the combination of IM with a NF Kappa B inhibitor (as thalidomide) contributes a new very interesting field of research. We treated 21 patients (11 female) with CML Ph +− resistant (n=13) or intolerant (n=8) to IM, mean +− SD age was 44 + 11 years. At diagnosis 16 (79%) were classified as high risk, according with Eutos scale. Mean +− SD time of IM treatment before adding thalidomide (100mg daily) was 47.8 +− 31 months. At the time of this preliminary analysis, mean follow up since thalidomide addition was 5 (1–18 months) and only 13 patients are evaluable for response (Global response rate was 76%): Six had hematological response & Four achieved complete cytogenetic response (CCgR). The first case was a 53 year old female, who started treatment with IM in accelerated phase, was intolerant to IM and neither achieve CCgR with IM, but reached it after 6 months of adding thalidomide and remains with this treatment after 18 months. The second case was a 38 year old female, who achieved CCgR after 6 months within IM treatment, lasted 53 months, and finally thalidomide was added after losing CCgR; she achieved a 2nd CCgR after 7 months with this combination, and continues with thalidomide at 11 months. The third one is a 44 year old female, who only achieved partial CCgR (pCGR), and after indicating thalidomide on accelerated phase, she had CCgR after 4 months of this drug and remains at 6 months of treatment. Finally, the fourth case is a 26 year old female that received thalidomide because of a suboptimal response to IM; she achieved CCgR after 2 months within thalidomide. Eight patients are not evaluable for response yet, but are ongoing and all will be detailed at ASH meeting. Toxicity has been acceptable, mainly grade 1 neurotoxicity & none severe adverse events have been documented. This is the first communication of the use of Thalidomide with Imatinib with promising results which may represent an alternative therapeutic in CML with antiproliferative enhancer and/or synergistic effect in patients with resistance to IM without opportunity of access to other treatments. This cases report open a future very interesting field of research in intolerance and resistance CML. Disclosures: No relevant conflicts of interest to declare.

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Monoclonal Gammopathy After Allogeneic Hematopoietic Stem Cell Transplant As a Marker For GvHD Onset

Blood ◽

10.1182/blood.v122.21.5484.5484 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5484-5484

Author(s):

Federico Monaco ◽

Francesco Zallio ◽

Gioacchino Catania ◽

Maria Teresa Corsetti ◽

Lia Mele ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Monoclonal Gammopathy ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Cell Transplant ◽

Post Transplantation ◽

Hematopoietic Stem ◽

The Past ◽

Non Hodgkin Lymphoma

Abstract Background/Aims Transient monoclonal gammopathy is a common alteration of laboratory test after allogeneic stem cells transplantation (alloBMT). However, until now, only scattered works have been published about it. The main paper reported on PubMed, regarding transient monoclonal gammopathy, was presented by the Dana Farber's group at the end of the eighties. The author of that paper showed an apparently strong correlation between development of graft versus host disease (GvHD) and appearance of a monoclonal gammopathy. Starting from that observation, we decided to evaluate among our allogeneic transplanted patients the incidence of M-component and its possible relationship with GvHD. Patient and Method 67 patients undergoing alloBMT at the Haematology Unit of Alessandria (Italy) between 2006 and 2010 were evaluated: 52% of patients were male and 48% were females. Pre-transplantation diagnosis included: 34 acute myeloid leukaemia (50.7%), 8 acute lymphoblastic leukaemia (11.9%), 7 non-Hodgkin Lymphoma (10.4%), 6 chronic leukaemia (9%), 4 myelodysplastic syndrome (6%), 2 Hodgkin lymphoma (3%) and 6 other less common malignancies (9%). All patients had, at least, two pre-transplantation serum electrophoresis with no evidence of pre-existing monoclonal component; for the analysis, we haven’t considered patients submitted to alloBMT for myeloma. Controls of serum electrophoresis were performed at 90, 180 and 360 days after transplantation. In our survey, 17 patients relapsed after alloBMT, 27 patients developed GvHD and 26 patients died. Post-transplantation follow up ranged from 81 to 2514 days with a median of 496 days. Results As a whole, 35/67 (52%) of the patients developed monoclonal gammopathy after transplantation. Comparing patients with or not monoclonal gammopathy after alloBMT, an increased GvHD development (54% vs 34%) and a decreased relapse incidence (19% vs 32%) was observed. Otherwise, analysing the appearance of monoclonal gammopathy at defined time-points, we have not detected any difference in overall survival, GvHD development, relapse incidence and post-transplantation mortality at +90 and +180 days post transplant. Vice versa, an increased GvHD development (50% vs 21% at median +378 days) was observed in patients with an appearance of monoclonal gammopathy at +360 days; so it seems that the presence of a M-component is associated only lately after 360 days to the possibility of GvHD development. Conclusion Evidence for monoclonal B-cell proliferation is common within the first year after alloBMT. The few papers published in the past found this proliferation more frequently associated with GVHD but without any long term adverse effect. Our data would seem to confirm a correlation between appearance of monoclonal gammopathy post-transplantation and GvHD development. In the past, the explanation for the evidence of a monoclonal gammopathy was associated to an aberrant immune reconstitution after alloBMT. Nevertheless in the last year it has been shown that B cells are involved in the pathogenesis of chronic GVHD (cGVHD) and anti-B-cell therapy can be used for the treatment of cGVHD. A prospective study with a larger population should be considered, in order to confirm our results and assay post-transplantation monoclonal gammopathy as an early marker for GvHD development. Disclosures: No relevant conflicts of interest to declare.

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Collection of Peripheral Blood Stem Cells in 118 Small Children Weighing 20 Kg or less: Experience of a Single Centre

Blood ◽

10.1182/blood.v128.22.3378.3378 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3378-3378

Author(s):

Jianyun Wen ◽

Yuelin He ◽

Libai Chen ◽

Jing Du ◽

Zhiyong Peng ◽

...

Keyword(s):

Stem Cells ◽

Peripheral Blood ◽

Conflicts Of Interest ◽

Thalassemia Major ◽

Median Number ◽

Peripheral Blood Stem Cells ◽

Hematopoietic Stem ◽

Small Children ◽

Cd34 Cells ◽

Blood Stem Cells

Abstract Background: Peripheral blood stem cells (PBSC) are increasingly used as a source of stem cells for either autologous or allogeneic hematopoietic transplantation in children.Although technically similar to adult procedures, PBSC harvest may be difficult in young children, especially in the very small children. Aim: In this study, we aimed to evaluatethe safety and efficacy of harvesting peripheral blood hematopoietic stem cells in very small children,and to provide a guideline. Methods: Between Jan 2013 to Mar 2016, we evaluated 118 children weighing 20 kg or less, with the smallest patient weighing 11 kg. The patients had a median age of 59 months and included 72 children with thalassemia major and 46 young donors. The granulocyte-colony stimulating factor (G-CSF) analogs were used at a dose of 10 mg/kg/day administered subcutaneously once a day and receiving oral calcium for five days before harvesting. Blood was withdrawn at a mean rate of 30-40 ml/min through a temporaryfemoral vein catheter (12 or 14 guage) to ensure adequate blood flow and returned through a larger catheter in a peripheral vein.Total nucleated cells(TNC) and CD34+ cells were estimated in the peripheral blood before collection of the apheresis product. Results: We collected sufficient products from all the children with one to three apheresis procedures. No serious complication was detected in all children and all aphereses were completed within 4 hours.The volume of blood per kilogram processed for each apheresis ranged from 55 to 160ml (median, 85ml). The median number of TNC and CD34+ cells collected were 12×108/kg and 15×106/kg per apheresis, respectively. Conclusions:We conclude that collection of PBSC is a safe and practical procedure in children, even in very small children. Disclosures No relevant conflicts of interest to declare.

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Gemtuzumab Ozogamicin After Allogeneic Stem Cell Transplantation for Acute Leukemia

Blood ◽

10.1182/blood.v120.21.1970.1970 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1970-1970

Author(s):

Takeshi Kobayashi ◽

Naoki Shingai ◽

Shuntaro Ikegawa ◽

Yukie Takahashi ◽

Jun Aoki ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Maintenance Therapy ◽

Cell Transplantation ◽

Salvage Therapy ◽

Conflicts Of Interest ◽

Initial Response ◽

Disease Recurrence ◽

Gemtuzumab Ozogamicin ◽

Hematopoietic Stem

Abstract Abstract 1970 Abstract Controversy abounds that anti-CD33 immunoconjugate, genutuzumab ozogamicin (GO) is really effective or not as a treatment for relapsed acute myeloid leukemia (AML). Consequently, GO is now commercially available in Japan, but not in USA or Europe. In this study, we have retrospectively analyzed the clinical impact of GO therapy as salvage or maintenance setting after allogeneic hematopoietic stem cell transplantation (allo-HSCT). During last 5 years, GO was given to 19 patients with AML as salvage therapy for disease recurrence (n = 15 patients) or maintenance therapy (n = 4 patients) after allo-HSCT in our institution. Clinical characteristics of these 19 patients are summarized (see Table): Median age was 44 years (range, 21–70 years). GO was basically administered at a dose of 3 mg/m2. The median cycle of GO therapy was 3 cycles (range, 1–12 cycles) and 3 cycles (range, 1–4 cycles) as salvage and maintenance therapy, respectively. GO was administered at a median of 205 days after allo-HSCT (range, 38–3,111 days) in the setting of salvage therapy, while as maintenance therapy, patients with high risk AML received GO as early as 29 days after allo-HSCT (range, 24–71 days). Two of 15 patients with recurrent disease achieved complete remission and 4 patients showed partial response (>50% decrease of bone marrow blast percentage). Thus, a total of 6 patients (40%) exhibited initial response to GO. However, 5 patients of them developed irreversible hepatic veno-occulusive disease (VOD) and eventually died at median of 146 days after GO therapy (range, 9–206 days). In view of 4 patients with maintenance therapy, 1 patient have faced to the subsequent disease relapse but no patients developed severe adverse effects including hepatic VOD and all patients are currently alive, albeit short follow-up. This small study demonstrates that GO offers an alternative tool for rescuing relapsed AML after allo-HSCT, but increases the risk of developing life-threatening hepatic VOD. Thus, further clarification is needed regarding which patients to treat with GO and at what dose of GO. Disclosures: No relevant conflicts of interest to declare.

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Mobilization Scheme With Cytarabine In Poor Mobilizers Patients Diagnosed With Lymphoma

Blood ◽

10.1182/blood.v122.21.5440.5440 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5440-5440

Author(s):

Cristina Calderón-Cabrera ◽

Magdalena Carmona González ◽

Jesús Martín ◽

Eduardo Ríos Herranz ◽

Pilar Noguerol Novella ◽

...

Keyword(s):

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cost Effective ◽

Median Number ◽

New Drugs ◽

Hematopoietic Progenitors ◽

Hematopoietic Stem ◽

Cutaneous Lymphomas ◽

Cd34 Cells

Abstract Introduction Mobilization regimens for hematopoietic stem cell transplantation have not undergone major changes except for the introduction of new drugs such as plerixafor. However, in patients receiving multiple lines of treatment, to obtain a suitable amount of hematopoietic progenitors (PH) is often difficult even with the addition of new drugs. We present our experience with a protocol of mobilization for poor mobilizer patients based on the use of cytarabine. Material and Methods From a total of 111 patients diagnosed with lymphoma who underwent autologous hematopoietic progenitors in our center from January 2005 to March 2013, 32 patients (35% of total) with previous mobilization failure, received cytarabine 400 mg/m2 /day x3 days + G-CSF (filgrastim or lenograstim) 10-16 mg /kg/day from day 7 to the end of collection. Cell blood cound and CD34 assays in peripheral blood were performed from day +11 postchemotherapy, and apheresis was started when CD34 > 10 x10e6/L. Results 30 patients had non-Hodgkin lymphoma (NHL) (13 diffuse large B-cell lymphoma, 7 mantle cell lymphoma, 5 follicular lymphoma, 2 MALT lymphoma, 1 angioimmunoblastic lymphoma, 2 cutaneous lymphomas) and 2 Hodgkin's lymphoma (HL). Median age was 49 years (range 27-67). Median number of treatment lines prior to mobilization was 3 (1-5). In all 30 patients with NHL, an adequate amount of CD34 + cells was obtained. Only one patient with HL, who had previously received 5 lines of chemotherapy, did not mobilize. The average time from the end of chemotherapy to start of apheresis was 13.7 days (12-20). The average number of CD34 + cells circulating the starting day of apheresis was 41/μL (11-109). The mean of apheresis performed was 1.8 (1-3) with an average amount of CD34 obtained of 4.69 x10e6/kg (1.5-6.8). All patients received outpatient treatment and only 2 required hospitalization: one for short-term neutropenic fever and another due to a limited cutaneous hemorrhage during the neutropenia phase. All patients were transplanted without incidence and successfully engrafted. None required G-CSF early postransplant. Conclusions Mobilization with intermediate-dose cytarabine has proven to be a cost-effective regimen in lymphoma patients with prior mobilization failure. Disclosures: No relevant conflicts of interest to declare.

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Venetoclax and DLI for Patients with Early Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation. a Historical Prospective Multicenter Trial

Blood ◽

10.1182/blood-2019-126999 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2018-2018

Author(s):

Odelia Amit ◽

Yael Bar-On ◽

Galit Perets ◽

Lena Atlas ◽

Liat Shargian ◽

...

Keyword(s):

Conflicts Of Interest ◽

Chronic Gvhd ◽

Univariate Analysis ◽

Tumor Lysis Syndrome ◽

Median Number ◽

Eligibility Criteria ◽

Hematopoietic Stem ◽

Early Relapse ◽

Allogeneic Hct ◽

Overall Response

Introduction: Prognosis in patients with post allogeneic HCT-early relapse of AML is dismal and response to salvage treatment is less than 20%. Venetoclax has been shown to be safe and efficacious in frail/elderly patients with AML. Treatment results in an increase of pro-apoptotic function, thus the addition of alloreactive T cells may augment the anti-leukemic potency. We hypothesized that the combination of donor lymphocyte infusion may further enhance this response. Methods: Eligibility criteria for this protocol were - age>18 y, early (<6 months post allogeneic HCT) relapse and no concurrent GVHD. Venetoclax was administered at a daily dose of 400 mg for up to 6 cycles with DLI in escalating doses for up to 4 doses. Additional chemotherapy was allowed according to physician discretion. Primary endpoint of study included assessment Overall response (CR/CRi/CRp) rate at 3 months post treatment. Secondary endpoints included 1-year OS, rate of acute and chronic GVHD, documented infections, hematological complications, and other safety measures. Results: From January 2017 until May 2019, 19 patients were given the study protocol. Median age was 60 (43-75) years, Table. There were no cases of tumor lysis syndrome. Microbiology documented infections occurred in 5 patients (26%) and 2 patients were admitted during protocol (10%). No cases of significant bleeding were observed, and majority of patients were able to tolerate the protocol without any admissions. Acute GVHD was observed in 2 (10%) patients and chronic GVHD was observed in 4 (21%) patients. Overall response was observed in 8 (47%) patients (CR, n=3; CRi, n=2; CRp, n=3). Median time to response was 28 (18-67) days (median number of courses 2 (1-6)) and duration of response was 106 (31-395) days. Survival at 6 months was 3.5 months (95% CI 1.5-5.5). Median survival of patients achieving complete remission was 16.2 months (CI not det.), Figure. On univariate analysis there was no association between patients and disease's characteristics and overall survival, however any type of GVHD (entered to the model as a time dependent variable) was associated with a lower rate of mortality (HR=0.2, p= .03). Conclusions: These results may endorse the hypothesis that enhancing alloreactivity as a therapy may lead to a chemotherapy free approach to relapsed AML. A phase 2 study is under preparation with a larger sample size and a standardized approach to additional salvage chemotherapy added versus Venetoclax + DLI regimen only for a more robust analysis of this therapeutic approach. Disclosures No relevant conflicts of interest to declare.

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Diagnosis and Treatment of Childhood Non-Hodgkin Lymphoma

Hematology ◽

10.1182/asheducation.v2007.1.285.0010285 ◽

2007 ◽

Vol 2007 (1) ◽

pp. 285-296

Author(s):

Alfred Reiter

Keyword(s):

Hodgkin Lymphoma ◽

Lymphoblastic Leukemia ◽

Treatment Options ◽

Treatment Strategies ◽

Large Cell ◽

Salvage Regimen ◽

Treatment Groups ◽

Non Hodgkin Lymphoma ◽

Appropriate Treatment ◽

New Treatment

Major advances have been made in the treatment of childhood non-Hodgkin lymphoma (NHL). The recognition that different NHL subtypes require different treatment strategies was fundamental to developing successful therapy regimens. Currently established therapy groups are lymphoblastic lymphoma (LBL) of precursor B- or T-cell type, mature B-cell neoplasms (B-NHL), and anaplastic large cell lymphoma (ALCL). Accurate diagnostic classification is crucial for allocating patients to appropriate treatment groups. Therapy protocols designed to treat children with acute lymphoblastic leukemia (ALL) have proven highly efficacious for treating children with LBL and are associated with event-free survival (EFS) rates up to 80%. For children with B-NHL, a strategy of rapidly repeated short, dose-intense courses proved more efficacious, with EFS rates up to 90%. In patients with ALCL, comparable results are achieved with either strategy, although this group has the highest relapse rate. The price of these efficacious treatments is considerable toxicity. On the other hand, the chance to survive after relapse is still dismal due to the almost complete lack of established salvage regimen. Thus, refinement of the balance between treatment burden and individual patient risk for failure is a major future task. A variety of new treatment options, some already established for treating adult NHL, await evaluation in childhood NHL.

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