Short Course Infliximab and Extracorporeal Photopheresis As Therapy For Steroid-Refractory Acute Gvhd In Matched Related and Unrelated Allogeneic Hematopoietic Cell Transplant (HCT)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4590-4590
Author(s):  
Jared Klein ◽  
James L Slack ◽  
Lisa Sproat ◽  
Veena Fauble ◽  
Nandita Khera ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Single Agent ◽  
Published Data ◽  
High Dose ◽  
Cell Transplant ◽  
Post Transplant ◽  
Allogeneic Hct ◽  
One Year ◽  
Grade Iii ◽  
Steroid Refractory

Background Steroid-refractory (SR) acute graft-versus host disease (aGVHD) is a serious complication of allogeneic HCT, for which there is no established standard treatment. Both ECP and cytokine inhibitors such as Infliximab have apparent single agent activity in the therapy of SR aGVHD, but there are no published data that address the efficacy of combination anticytokine therapy and ECP in this setting. We report here results in 18 adult patients (pts) with grade III or IV SR aGVHD who were treated with concurrent Infliximab and ECP. Patients All pts underwent allogeneic HCT (first transplant, n=15, second transplant, n=3) for a hematologic malignancy at Mayo Clinic Arizona between March 2012 and May 2013. The median age was 61 (range 22-70), and the median follow-up of 6 surviving pts is 263 days (range 79-433). Donors were related in 3, matched unrelated in 8, and mismatched unrelated in 7. GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil in 13 pts and tacrolimus/methotrexate in 5; in addition, 17 pts received in vivo T-cell depletion with Thymoglobulin 2.5 – 7.5 mg/kg. All pts developed grades III-IV aGVHD at a median day 27 post-transplant (range 10-107) and failed to respond to a course of high-dose corticosteroids (methylprednisolone or equivalent 2 mg/kg daily) for at least 5 days. Treatment Regimen At diagnosis of SR aGVHD, pts were scheduled to receive weekly Infliximab 10 mg/kg (maximum 4 doses), concurrent with ECP performed twice or thrice weekly for one month, followed by a pre-specified taper schedule (anticipated total treatment duration of 6-9 months). To minimize infectious risk and morbidity, corticosteroids were tapered rapidly after the start of Infliximab/ECP therapy. Results Thirteen pts (72%) responded to the Infliximab/ECP combination; complete response (CR; resolution of all GVHD symptoms for at least 30 days and able to discontinue corticosteroids) was observed in 6 pts (33%), and partial response (PR; improvement in GVHD symptoms, partial taper of corticosteroids, and no additional agent for at least 30 days) in 7 pts (39%). At the time of this report, 6 pts are alive, and the Kaplan-Meier estimate of one-year survival is 22.5 % (95% CI, 8.8%-47%). Only pts who achieved CR had good outcomes (5/6 surviving and clinically well); among 13 pts with PR (7) or no response/progression (6) to Infliximab/ECP, 12 have died and one is day 79 post transplant and remains on ECP and low-dose prednisone. Eleven of the 12 deaths were related to GVHD or complications of its treatment (infection, multi-organ failure). Conclusions In this retrospective study of adult pts with severe (grade III/IV) SR aGVHD, treatment with 4 doses of weekly Infliximab and concurrent ECP resulted in an overall response rate of 72%, with one-third of pts achieving CR; the regimen was well-tolerated and facilitated early taper and rapid discontinuance of corticosteroids. Unfortunately, the overall survival of 22.5% at one year does not appear superior to other single agent or combination therapies reported in the literature, or to historical data from our program. Although a small percentage of pts appear to be long-term survivors, the majority of pts succumb to complications of progressive GVHD or infection. Given poor results with available therapies, and the dismal prognosis of pts with SR aGVHD, future research should focus on better preventative strategies for this devastating complication of allogeneic HCT. Disclosures: No relevant conflicts of interest to declare.

Characteristics and Outcome of Patients with Acute Myeloid Leukemia (AML) Refractory to One Cycle of High Dose Cytarabine-Based Induction Chemotherapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1038-1038
Author(s):  
Farhad Ravandi ◽  
Jorge Cortes ◽  
Stefan Faderl ◽  
Susan O'Brien ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conflicts Of Interest ◽  
Single Agent ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Refractory Disease ◽  
Allogeneic Stem Cell Transplant

Abstract Abstract 1038 Poster Board I-60 Background: Outcome of patients (pts) with AML refractory to initial induction is assumed to be poor but the available data is limited. Furthermore, pts refractory to standard dose cytarabine-based regimens may be salvaged with high dose ara-C (HiDaC, defined as daily ara-C dose ≥ 1 g/m2). Information on the outcome of pts refractory to initial HiDaC - based induction is more limited. Aim To better characterize predictors of poor response to HiDaC-based induction and to evaluate the outcome of pts refractory to such induction regimens. Methods: We identified pts treated with induction regimens containing HiDaC at the University of Texas – M D Anderson Cancer Center who did not achieve a compete remission (CR) after one cycle of induction. We examined their pre-treatment characteristics and compared them with similar pts achieving a CR. We also examined their response to salvage chemotherapy and outcome. Results: Among 1179 pts treated with HiDaC-based induction therapy from 1995 to 2009, 285 were primary refractory to one course of induction. Their median age was 59 (range, 18 - 85). Median pretreatment WBC was 9.0 × 109/L (range, 0.3 – 394 × 109/L). Cytogenetics included-5/-7/complex 101 (35%), diploid 85 (30%), other intermediate 98 (34%), favorable 1 (<1%). 165 (58%) pts had antecedent hematological disorder. Induction regimens used included HiDaC with anthracyclines (n=181, 64%), HiDaC with non-anthracycline chemotherapy (fludarabine, clofarabine, topotecan, and troxacitabine) (n=104, 36%) Pts with primary refractory disease were older (Median age 59 vs. 56; p=000004), more likely to have chromosome 5/7 or complex cytogenetic abnormalities (P=0.0001), more likely to have AHD (p=0.0001), and had a higher presentation WBC (P=0.036), but not a higher incidence of FLT3 mutations (p=0.85) than those achieving CR. Primary refractory disease was not more likely with non-anthracycline containing regimens than those with anthracyclines (p=0.58). Salvage chemotherapy included combination chemotherapy in 111 (39%)(non-ara-C regimen in 40, containing ara-C in 71), single agent chemotherapy in 64 (22%), allogeneic stem cell transplant in 22 (8%) and none in 88 (31%). Forty-three (15%) pts responded to salvage including 35 CR and 8 CRp. 114 (58%) pts were resistant and 35 (18%) died; 5 (3%) were lost to follow-up. With a median follow-up of 115 weeks (range 8 – 347 weeks) in pts responding to salvage, 21 pts (7%) were alive and in CR, for at least 6 months including 14 who underwent an allogeneic stem cell transplant (median overall survival for these 21 pts, 30 months; range, 13 to 87 months). Conclusions: Outcome of pts with disease refractory to HiDaC-based induction is poor. Alternative strategies are needed in these pts who are likely to be resistant to standard chemotherapy. Disclosures: No relevant conflicts of interest to declare.

Enrichment of Allogeneic Tumor Antigen-Specific T Cells From Bone Marrow (BM) of Patients Treated with High-Dose Post-Transplant Cyclophoshamide (Cy) – A Novel Approach to Adoptive Immunotherapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 647-647
Author(s):  
Kimberly Noonan ◽  
Leo Luznik ◽  
Ivan M. Borrello
Keyword(s):  
T Cells ◽  
Adoptive Immunotherapy ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Single Agent ◽  
Hematologic Malignancies ◽  
High Dose ◽  
Post Transplant ◽  
Novel Approach ◽  
Tumor Specificity

Abstract Abstract 647 Background: Donor lymphocyte infusions (DLI) has limited efficacy and is associated with substantial graft vs host disease (GVHD) in treating relapse after allogeneic BMT (alloBMT) in large part due to the absence of significant tumor specificity. Thus, novel strategies are required that increase the tumor specificity with reduced alloreactivity. High-dose Cy post-BMT effectively reduces GVHD through early elimination of allo-reactive T cells and enables immune reconstitution free of ongoing pharmacologic immunosuppression. Since the BM is both the site of disease in most hematologic malignancies and a reservoir of tumor specific T cells, we hypothesized that marrow infiltrating lymphocytes (MILs) collected after alloBMT in patients treated with high-dose Cy could be a source of tumor-specific T cells for adoptive immunotherapy. Methods: BM was obtained from patients 2 –12 months after HLA-matched alloBMT on the clinical trial using high-dose post-transplant Cy as a single agent GVHD prophylaxis. The MILs were activated and expanded with CD3/CD28 antibody-coated beads. Results: Allo-MILs can be reproducibly expanded (574-fold avg expansion; 14–2000) at all time points tested. The activated allo-MILs are not anergic, exhibit anti-HLA-reactivity against third party allo-antigens but do not respond to recipient allo-antigens. Tumor-specific MILs were significantly expanded as determined by reactivity to HL60/K562 myeloid cell lysates (P<0.0001; pre- vs. post-activation). In contrast, no change was observed in cultures pulsed with irrelevant antigens, thus suggesting the specificity of the response. The ability to expand allogeneic antigen-specific MILs was also confirmed with a 15.5 fold expansion of PR-1 specific (HLA) A*0201-restricted CD8+ T-cells using tetramers. Conclusions: We can augment the tumor-specificity of MILs obtained post-transplant with minimal allo-reactivity in patients treated with post-BMT high-dose Cy. This could represent a novel approach to highly tumor-specific DLI. A phase I/II trial is planned to assess the safety and feasibility of administering ex vivo expanded post-transplant, allogeneic MILs to patients with relapsed hematologic malignancies after alloHSCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Double-Stranded DNA (dsDNA) Viral Infections Among Allogeneic Hematopoietic Cell Transplant (HCT) Recipients in the First Year after Transplant

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3296-3296 ◽  
Author(s):  
Vernon F Schabert ◽  
Essy Mozaffari ◽  
Yi-Chien Lee ◽  
Roman Casciano
Keyword(s):  
Viral Infection ◽  
Viral Infections ◽  
Bk Virus ◽  
First Year ◽  
Cell Transplant ◽  
Post Transplant ◽  
Allogeneic Hct ◽  
Barr Virus ◽  
Epstein Barr ◽  
One Year

Abstract Introduction: Double-stranded DNA (dsDNA) viral infections (including cytomegalovirus, adenoviruses, BK virus, and Epstein-Barr virus) can lead to significant morbidity and mortality among immunocompromised patients following allogeneic hematopoietic stem cell transplant (HCT). The lack of a broad-spectrum antiviral with the safety and tolerability to prevent viral infections poses management challenges for patients at risk of multiple dsDNA viral infections. Using a large US insurance claims database, this study describes the incidence of dsDNA viral infections and co-infections among allogeneic HCT recipients. Methods: The MarketScan Research Databases were used to identify commercial and Medicare enrollees with an ICD-9 or CPT procedure code for an allogeneic HCT between 7/1/2009 and 6/30/2014. Eligible patients were required to have 365 days of health plan enrollment prior to HCT, but no minimum enrollment was required post-HCT. Incidence of cytomegalovirus (CMV), adenovirus (AdV), BK virus, Epstein-Barr virus, herpes simplex, varicella zoster, and other dsDNA virus infection was measured from the date of the transplant until one year post-transplant. The rates of infection with two dsDNA viral infections or three or more dsDNA viral infections were assessed, and in-hospital mortality or transfer to hospice services within one year of transplant was reported by the number of observed dsDNA viral infection. Results: We identified 3,035 allogeneic HCT patients (mean age 47.3 years, 56.9% male), including 30.4% (n=924) with at least one dsDNA viral infection within the first year post-transplant. Of these, 69.2% had CMV infection (n=639), 5.4% had AdV infection (n=50), and 10.3% had BK virus infection (n=95). Among patients with a reported dsDNA viral infection, 17.6% (n=163) had more than one dsDNA viral infection, including 14.6% (n=135) with two dsDNA viral infections and 3.0% (n=28) with three or more viral infections. A statistically significant increase in the rate of in-hospital death or transfer to hospice within the first year post-transplant was observed for patients with reported dsDNA viral infection vs those without. Specifically, the rate of in-hospital mortality/transfer to hospice increased from 14.9% (315/2111) for patients without a reported dsDNA viral infection to 19.2% (146/761, p=0.0060) with one dsDNA viral infection, 23.0% (31/135, p=0.0121) for patients with two dsDNA viral infections, and 35.7% (10/28, p=0.0023) for patients with three or more dsDNA viral infections. Conclusions: A substantial proportion of allogeneic HCT recipients with a dsDNA viral infection have two or more dsDNA viral infections. Diagnoses on insurance claims may underestimate true incidence of dsDNA viral infection and co-infection. Mortality risk increases significantly with the number of dsDNA viral infections. Availability of a safe and well-tolerated broad spectrum antiviral for prevention of primary or reactivation infections could potentially reduce the morbidity and mortality associated with dsDNA viral infections and their significant sequelae. Disclosures Schabert: LASER Analytica: Employment. Mozaffari:Chimerix Inc.: Employment, Equity Ownership. Lee:LASER Analytica: Employment. Casciano:LASER Analytica: Employment.

scholarly journals Efficacy and Toxicity of Treatments for Primary Central System Lymphoma: Review of the Recent Literature

2019 ◽  
Vol 9 (1) ◽  
pp. 61-67
Author(s):  
Mohammad Jay ◽  
David. A. MacDonald
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Survival Benefit ◽  
Radiation Treatment ◽  
Single Agent ◽  
Central Nervous System Lymphoma ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Wide Range

Primary Central Nervous system lymphoma (PCNSL) is an uncommon type of central nervous system lymphoma, most commonly presenting as hemiparesis and headache. Currently, there is a wide range of treatments for PCNSL, consisting of various permutations between chemotherapy, radiation and autologous stem cell transplant (ASCT). Although the backbone of PCNSL treatment consists of High-dose Methotrexate (HD-MTX), the role of combination versus single agent chemotherapy, combined modality (chemotherapy + radiation) versus chemotherapy or radiation alone, and the use of consolidative ASCT are contested. Surgery does not have a role in the treatment of PCNSL although stereotactic biopsies tend to help with symptomatic relief. Radiation monotherapy is generally reserved for patients with contraindications to chemotherapy or as a palliative measure. Combined chemotherapy and radiation treatment has been shown to have a great efficacy, although its increased neurotoxicity compared to chemotherapy alone is a major drawback. A growing body of research is focused on comparing the efficacy of various chemotherapeutic regimens. Currently, the MATRix regimen comprising of HD-MTX(3.5g/m2)-cytarabine/rituximab/thiotepa is widely used. The additional survival benefit of ASCT is contested although its role in the treatment of refractory or relapsed PCNSL is generally agreed upon. Finally, intrathecal HD-MTX has been shown to have added survival benefit when added to the standard therapies. Further retrospective and prospective studies are required to compare the efficacy and toxicity of various treatment options, with a focus on different chemotherapeutic agents and ASCT.

Steroid Refractory Acute and Chronic Graft Versus Host Disease (GVHD) - Response to Photophoresis+/− Rituximab.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5358-5358 ◽  
Author(s):  
Ramakrishnan Parameswaran ◽  
Maggie Sekeramayi ◽  
Kelly McCaul ◽  
Bill Bradfeldt
Keyword(s):  
Stem Cell ◽  
Acute Gvhd ◽  
Hemorrhagic Cystitis ◽  
Chronic Gvhd ◽  
Bk Virus ◽  
High Dose ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Gi Tract ◽  
Steroid Refractory

Abstract Acute GVHD is an important complication following hematopoeitic stem cell transplantation (HSCT), with significant attendant morbidity and mortality. High dose steroids remain the cornerstone of therapy. Steroid refractory GVHD carries a very poor prognosis. Various therapies are available for steroid refractory acute GVHD, but response is not uniform. Among the less intensive regimens, extracorporeal photopheresis (ECP) and rituximab, a chimeric humanized anti CD 20 monoclonal antibody have been shown to be useful in treating refractory acute and chronic GVHD. We describe 8 patients who developed GVHD following transplantation of HLA-identical stem cells, from siblings in 7 and from an unrelated donor in one. 2 patients had steroid refractory chronic GVHD of the liver, 3 patients had a refractory chronic GVHD of the skin and one had a steroid responsive restrictive pulmonary syndrome. Of the patients with skin GVHD, 2 had chronic scelrodermatous GVHD, which was of 20 years duration in one patient and 8 in the other. 2 patients had acute GVHD of the GI tract. The age range was 21– 53 years. All patients were in complete remission from their primary disease at the time of therapy for GVHD. 3 patients had a diagnosis of acute lymphoblasitc leukemia and 5 acute myeloid leukemia All had failed treatment with high dose steroids and/or tacrolimus and/or cellcept, and, one had also failed ATG therapy. Then therapy for refractory GVHD was initiated with rituximab in 3 patients and with photopheresis in 5. 7 patients received ECP. One patient with refractory chronic GVHD of the liver received rituximab alone in addition of steroids and tacrolimus. The patients with acute GVHD were treated with daily ECP for 10 days and then were weaned down to two procedures every 2 weeks. Patients with chronic GVHD received ECP 2 to 3 times a week for 6 weeks and were subsequently similarly weaned down. In the patients with acute GVHD of the GI tract complete responses occurred at 10 days in one patient and 45 days in the second as determined by complete cessation of diarrhea, cramps and nausea. Both patients with chronic GVHD of the liver achieved normalization of the serum bilirubin by 26 and 38 days after initiation of therapy. All patients tolerated successful taper of steroid therapy. The two patients with sclerodermatous GVHD have shown marked improvement in skin texture and range of motion at the involved joints. The patient with the pulmonary symptoms has shown complete normalization of pulmonary function. 5 patients were at risk of CMV reactivation, but failed to do so. One patient developed BK virus associated hemorrhagic cystitis that required therapy with cidofovir. There were 3 admissions for neutropenic fever, three for pneumonia and one each for gastroenteritis, HSV gingivostomatitis and line related sepsis. Two patients had line related thrombosis. None of the patients had relapse of their disease. 2 of the responders had an ECOG performance status 2, two of 3, one of 4 and four of &lt;/= 1 while being treated. All patients demonstrated improvement in functional status. ECP and rituximab is a well tolerated and effective modality for therapy of steroid refractory chronic and acute GVHD in both related and unrelated marrow stem cell transplant recipients.

Prospective Oral Mucositis Audit (POMA): Occurrence and Consequences of Severe Oral Mucositis in High Dose Melphalan and BEAM Conditioning.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 46-46
Author(s):  
Nicole N.A. Blijlevens ◽  
Shaun McCann ◽  
Pam Bacon ◽  
Roisín Cinnéide ◽  
Barry Quinn ◽  
...  
Keyword(s):  
Length Of Stay ◽  
Oral Mucositis ◽  
Resource Use ◽  
Well Being ◽  
High Dose ◽  
Routine Practice ◽  
Cell Transplant ◽  
Oral Toxicity ◽  
Post Transplant ◽  
High Dose Melphalan

Abstract Oral mucositis (OM) is an adverse effect of myeloablative regimens which seriously affects patient well-being and may increase risk of systemic infection and delay recovery. Trial-based reports of OM occurrence vary widely, with evidence of underreporting, and data on the incidence and impact of OM in routine practice are limited. Initiated by the European Group for Blood and Marrow Transplantation, this study observed pts. with multiple myeloma (MM) or non-Hodgkin lymphoma (NHL) from 25 transplant centres across 13 European countries, receiving high dose melphalan or BEAM followed by autologous stem-cell transplant. Aims were to assess duration and incidence of severe (WHO oral toxicity scale Grade III–IV) OM and ulcerative (Grade II–IV) OM, medical resource use for OM prevention and treatment, and associations with infection and duration of hospitalisation. Prospective OM assessments were conducted daily from the start of conditioning until 30 days post transplant or hospital discharge. To achieve high and consistent quality of OM assessment, nurse assessors underwent a multimedia-assisted face-to-face training before study initiation. Of 197 evaluable pts., 110 (56%) had MM and 87 (44%) had NHL. Mean age at enrolment ± SD was 57 ± 8 years for MM and 50 ± 13 years for NHL. Women accounted for 36% of the MM sample and 51% of the NHL sample. In both sub-samples, 94% of pts. had ECOG status ≤ 1. The incidence of severe OM was 46% (95% CI 37–56%) for MM and 41% (95% CI 31–52%) for NHL. Severe OM episodes had a mean duration of 5.4 ± 3.3 days (95% CI 4.6–6.3 days) in MM and 5.3 ± 3.2 days (95% CI 4.3–6.4 days) in NHL. Ulcerative OM occurred in 67% (95% CI 58–76%) of MM pts. and 60% (95% CI 49–70%) of NHL pts., with a mean duration of 6.6 ± 4.4 days (95% CI 5.6–7.6 days) and 6.5 ± 3.8 days (95% CI 5.6–7.7 days), respectively. WHO scale results and indicators of specific OM symptoms showed very similar temporal patterns, reaching their maximum around day 12 after the start of conditioning in both groups. Clinically relevant associations with type of disease/conditioning or gender were not detected. A non-statistically significant trend hinted at an association of OM duration with age. The incidence of fever ≥ 38° C was 68% in pts. with severe OM vs. 47% in pts. without (univariate p = 0.004; odds ratio 2.4, 95% CI 1.3–4.4). Mean length of stay ± SD (truncated at 30 days post transplant) was 21.1 ± 4.0 days in pts. with severe OM vs. 19.9 ± 4.8 days in pts. without (univariate p = 0.023). Preliminary multivariate analysis adjusting for other potential predictors confirmed these effects. Based on a close collaboration of nurses and physicians, this study showed severe OM to be a substantial clinical problem in pts. receiving high dose melphalan or BEAM conditioning chemotherapy. Associations with fever occurrence and length of stay indicate potentially harmful clinical sequelae and relevant economic consequences. Associations with confirmed infection, and resource use for OM management, remain to be assessed.

Rituximab in Combination with High-Dose Steroids in Advanced, Refractory Chronic Lymphocytic Leukaemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4719-4719
Author(s):  
John Quinn ◽  
Sajir Mohamedbhai ◽  
Marilyn Treacey ◽  
Shirley D’Sa ◽  
Amit Nathwani
Keyword(s):  
Stem Cell ◽  
Chronic Lymphocytic Leukaemia ◽  
Stem Cell Transplant ◽  
Lymphocytic Leukaemia ◽  
Median Number ◽  
High Dose ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Post Transplant ◽  
Reduced Intensity

Abstract High-dose methlyprednislone (HDMP) is active in refractory chronic lymphocytic leukaemia (CLL), and rituximab, although showing limited efficacy as a single agent, is effective when used in combination with other cytotoxic agents. Early relapse (<12 months) after purine-analogue based treatment poses a difficult management problem as older patients may be unable to tolerate treatment intensification. This retrospective audit examines the outcome in patients with advanced, refractory/relapsed CLL treated with a combination of high-dose steroids and rituximab. Eleven patients with CLL were treated with rituximab (375mg/m2) and high-dose steroids between 2003 and 2007. Ten patients had advanced and/or refractory disease and one patient had severe autoimmune haemolytic anaemia complicating early-stage CLL. Median age was 70 (range 54–82) and there were 7 male and 4 female patients. Nine patients had Binet stage C disease. Six of the 7 patients for whom results were available had germ-line variable heavy chain immunoglobuliun genes. Median number of prior treatments was 2 (range 1–6) with 9 patients having already received a fludarabine based-regimen. Six patients received a combination of rituximab and high-dose methylprednisolone (1gm/m2 on days 1–5) and 5 patients received a combination of rituximab and high-dose dexamethasone (40mg daily on days 1–4) and. Cycles were repeated every 28 days and the median number of cycles received was 4 (3–6). Antiviral and anti-PCP prophlaxis with aciclovir and co-trimoxazole was routinely prescribed. Response was assessed according to the NCI working group criteria. There was one complete response (CR) and 7 partial responses (PR). Furthermore, 2 of the patients who achieved a PR were successfully salvaged prior to reduced-intensity allogeneic stem-cell transplant and both remain in complete remission (CR) post-transplant. The other 3 patients had minor responses that did not meet NCI response criteria. Median duration of response was 13 months (6–35), excluding the 2 patients who received allogeneic transplants. Three patients required hospital admission with infective complications during treatment. No other significant toxicity was observed. 3 patients have died, none of whom had attained a PR. In conclusion, we found that rituximab in combination with high-dose steroids is a safe and well-tolerated combination in patients with advanced refractory CLL. One patient achieved a CR and we observed a PR in 7/11 patients. Importantly, 2 of these patients were successfully salvaged prior to reduced-intensity conditioning allogeneic stem-cell transplant and both remain in CR at 4 and 12 months respectively post-transplant.

Long Term Outcomes for Patient with Diffuse Large B-Cell (DLBCL) or Hodgkin’s Lymphoma (HL) following Autologous Stem Cell Transplant (ASCT) Who Are Disease Free at Five Years Post Transplant.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2146-2146
Author(s):  
Julie M. Vose ◽  
Fausto Loberiza ◽  
Philip Bierman ◽  
Robert Bociek ◽  
James Armitage
Keyword(s):  
Organ Dysfunction ◽  
Secondary Malignancy ◽  
High Dose ◽  
Cell Transplant ◽  
Secondary Malignancies ◽  
Long Term Outcome ◽  
Cox Regression Analysis ◽  
Post Transplant ◽  
Disease Free

Abstract From 1984–2002, 294 patients (pts) with DLCL and 436 pts with HL (total 730) received high dose chemotherapy and ASCT at the University of Nebraska Medical Center. This analysis evaluates the long term outcome for pts in those cohorts who survived for five years and remained progression-free (PFS) during that interval with no further therapy. There were 92 pts with DLCL and 121 with HL who were alive and disease-free at 5 years post-transplant. The median age for pts with DLBL was 44 yrs (range 17–70) and 32 yrs (range 15–62) for pts with HL at the time of transplant. The median time to transplant from the time of diagnosis was 11 months (mo) for the DLCL group and 32 mos for HL pts. The majority of pts were chemo sensitive at the time of transplant – 80% for DLCL and 70% for HL. The median follow-up among survivors was 98 mo (range 61–222) for DLCL pts and 127 mo (range 63 – 272) for HL pts. The outcomes are as follows: Variables DLCL HL p-value PFS @ 10 yrs 89% 82% 0.26 OS @ 10 yrs 91% 90% 0.72 Secondary Malignancies 11 (12%) 21 (17%) 0.26 Figure Figure Cox regression analysis showed only age (&gt; 60 yrs) at the time of transplant was associated with an increased relative risk (RR) of death; 7.64 (2.61–22.35) compared to pts &lt; 40 yrs. Pts with DLCL had a RR of progression 0.12 (0.02–0.89) as compared to those with HL. Causes of death are as follows: Secondary malignancy 14 (41%) Disease progression 7 (20%) Organ dysfunction 8 (24%) Infection 2 (6%) Unknown 3 (9%) Conclusions: Patients with DLCL and HL who are progression-free at five years post-transplant have a low risk of relapse of their lymphoma. However, secondary malignancies and organ dysfunction are a long term risk from ASCT and survivors should be carefully followed for these complications.

Alemtuzumab-Containing Allogeneic Hematopoietic Cell Transplant (HCT) for Relapsed Lymphomas: Prognostic Factors and Outcome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2247-2247
Author(s):  
Vaishalee P. Kenkre ◽  
Sarah Horowitz ◽  
Sonali M. Smith ◽  
Andrew Artz ◽  
Kenneth S. Cohen ◽  
...  
Keyword(s):  
B Cell ◽  
Single Agent ◽  
Salvage Chemotherapy ◽  
Low Grade ◽  
Cell Transplant ◽  
Refractory Disease ◽  
Off Label Use ◽  
Off Label ◽  
Allogeneic Hct ◽  
Label Use

Abstract Abstract 2247 Poster Board II-224 The role of allogeneic HCT for relapsed lymphomas remains imprecisely defined. Most pts considered for alloHCT are heavily pretreated and many have failed a prior autologous HCT. At The University of Chicago, 69 lymphoma pts (median age 54; range, 24-70) underwent allogeneic HCT after alemtuzumab-containing reduced intensity conditioning (RIC) regimens between 11/01 and 6/09. Ten had Hodgkin lymphoma (HL), 23 low-grade B-cell NHL (LGL), 17 intermediate-grade B-cell NHL (IGL), 9 mantle cell lymphoma (MCL), and 10 T-cell NHL (TCL). 25 pts (36%) had refractory disease and 17 pts (25%) had elevated LDH. Pre-HCT PET scans were performed in 48 pts and 31 (65%) were PET positive. Performance status (PS) was 0 for 45 pts (70%) and 1 for 18 pts (28%). 19 pts (27%) had failed a prior autologous transplant, and 4 pts had failed a prior allogeneic transplant. 31 pts (45%) had unrelated and 38 (55%) related donors. Conditioning regimens along with alemtuzumab included: fludarabine/melphalan (n = 40), clofarabine/melphalan (n = 20), fludarabine/busulfan (n = 5), and thiotepa/busulfan/cyclophosphamide (n = 4). GVHD prophylaxis consisted of single agent tacrolimus in all patients. With a median follow-up for survivors of 22 mos (range 2-94 mos), 2 yr overall survival (OS) is 53% (95%CI, 40-66). Progression-free survival (PFS) is 46% (95%CI, 34-58) at 1 yr and 38% (95%CI, 28-50) at 2 yrs. 11 pts had grade II-IV aGVHD and transplant-related mortality (TRM) was 20% at 1 yr. Disease responsiveness to salvage chemotherapy prior to transplant (as determined by CT scan) was highly predictive of PFS (p = 0.03). Pts with chemo-sensitive disease had a 2 yr PFS of 44% (95%CI, 28-60), those with chemo-refractory disease 30% (95% CI, 10-50). 2 yr PFS was 52% (95%CI, 30-74%) for LGL, 48% (95%CI, 12-84) for MCL, 28% (95%CI, 6-50) for IGL, 30% (95%CI, 0-60) for HL, and 34% (95%CI, 6-66) for TCL. Patient age, pre-transplant LDH, PS (0 vs 1), prior auto, donor type, and conditioning regimen did not correlate with outcome. Interestingly, a positive vs negative pre-HCT PET also did not correlate with outcome (p = 0.21). 23 pts (33%) relapsed. 13 of those have died, 2 are alive with disease, and 8 are in a durable subsequent remission lasting a median of 46 mos (range 8-69) after further chemotherapy (n=6) or DLI (n=2). Durable subsequent remissions were more common in those with late relapses (>6 mos after transplant) (Fig 1). Conclusion: Chemosensitivity by conventional CT scans remains the most important predictor of outcome. In contrast to other reports, neither the pre-HCT PET nor LDH correlate with outcome. Patients relapsing > 6 mos after alloHCT can re-enter durable remissions with chemotherapy alone. This suggests a favorable interaction between a persisting donor graft and salvage chemotherapy. Disclosures: Off Label Use: off-label use of clofarabine and alemtuzumab. Kline:Genzyme corporation: Membership on an entity's Board of Directors or advisory committees. Stock:Genzyme: Research Funding.

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