Daclizumab Therapy Improves Outcome in Steroid Refractory Acute Graft Versus Host Disease (aGVHD).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5092-5092
Author(s):  
Richard T. Doocey ◽  
Matthew J. Greenwood ◽  
Dawn Warkentin ◽  
Kevin W. Song ◽  
Alan Le ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Gvhd ◽  
Interleukin 2 ◽  
Complete Response ◽  
Cell Transplant ◽  
Phase Ii Trials ◽  
Term Survival ◽  
Post Transplant ◽  
Steroid Refractory

Abstract Steroid refractory aGVHD following allogeneic stem cell transplant (SCT) is associated with a long-term event-free survival (EFS) of less than 20%. Daclizumab is a humanised monoclonal antibody specific for the Tac subunit of the Interleukin-2 (IL-2) receptor. It inhibits IL-2 binding and is thought to be more specific for alloreactive lymphocytes than pan-T cell antibodies. Limited phase II trials using daclizumab for steroid refractory aGVHD have demonstrated 50–60% complete response (CR) rates, though its safety and efficacy as primary aGVHD treatment has recently been questioned. We examined the Vancouver experience with daclizumab in the management of steroid refractory aGVHD. Between 8/00 and 2/04, 35 patients with steroid refractory aGVHD were treated with daclizumab. Male:female ratio was 1.7:1. Median age was 42 years (17–53). Pretransplant diagnoses were AML (n=7), ALL (n=6), CML (n=6), MDS (n=5), NHL (n=6), MM (n=4) and Myelofibrosis (n=1). One patient with relapsed AML post-SCT developed aGVHD following DLI. Stem cell source was matched unrelated bone marrow (BM) (n=11) or peripheral blood (PB) (n=8), mismatched unrelated BM (n=6) or PB (n=3), matched related BM (n=2) or PB (n=4), and mismatched related BM (n=1). Twenty eight pts were conditioned with Cyclophosphamide/TBI. CSP/MTX aGVHD prophylaxis was used in all pts and initial aGVHD therapy consisted of Methylprednisolone 2 mg/kg IV. Grade I-II aGVHD developed in 18/35 (51%) pts and grade III-IV in 17/35 (49%) pts. Median onset of aGVHD was 18 (6–49) days post transplant. Steroid refractory pts received daclizumab 1 mg/kg IV (maximum dose 100mg) on days 1, 4, 8, 15 and 22 at a median of 40 (18–94) days post transplant. Daclizumab response was assessed at day 42 following its initiation. A CR was defined as a return to stage/grade 0 aGVHD and a PR as a reduction of ≥ 1 aGVHD stage/grade without need for additional therapy. There were no significant infusional complications. One patient died during the response assessment period (regimen related pulmonary toxicity). Overall response rate (ORR) was 25/35 (73%), with 15/25 (44%) achieving a CR and 10/25 (29%) a PR. Response was most likely in pts with skin involvement. ORGAN ORR CR PR NR SKIN 25/33 (76%) 18/33 (55%) 7/33 (21%) 8/33 (24%) GUT 15/23 (65%) 7/23 (30%) 8/23 (35%) 8/23 (35%) LIVER 8/14 (57%) 3/14 (21%) 5/14 (36%) 6/14 (23%) SKIN ALONE 9/11 (82%) 8/11 (73%) 1/11 (9%) 2/11 (18%) Twenty four (68%) pts developed limited (n=8) or extensive (n=15) chronic GVHD. The 3-year OS and EFS rates were 35% (95% CI 17–53%) and 28% (95% CI 12–47%), respectively. Female patients had a significantly poorer OS (p=0.0064) and EFS (p=0.0112) as did those pts receiving SCT from female donors (p=.0333 / 0.0456). Eleven patients (31%) received antithymocyte globulin (ATG) in addition to daclizumab. In this subgroup, aGVHD response was more likely but ATG treated patients had increased CMV antigenemia rates during the treatment response period (p=0.01), and a significantly lower EFS (p=0.0064) and OS (p=0.0123). Daclizumab is an effective agent for steroid refractory aGVHD especially if limted to the skin. Long-term survival appears to be superior in pts treated with this agent although its use along with ATG may compromise pt outcome.

Long-Term Survival In Patients With Acute Steroid Refractory Graft-Versus-Host-Disease (SR-GVHD) Treated With Infliximab Combined With Daclizumab

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4624-4624
Author(s):  
Sanaz Nicky Soltani ◽  
Ramaprasad Srinivasan ◽  
Theresa Jerussi ◽  
A. John Barrett ◽  
Thomas E Hughes ◽  
...  
Keyword(s):  
High Probability ◽  
Chronic Gvhd ◽  
Complete Response ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival ◽  
Post Transplant

Acute SR-GVHD occurs in approximately 15% of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), and is associated with a 70-90% long-term mortality rate. We previously reported that concomitant blockade of TNF-α and IL-2 pathways with infliximab combined with daclizumab have a synergistic therapeutic effect, with a high probability of complete resolution of SR-GVHD. Although various treatment modalities are effective in the treatment of SR-GVHD, minimal long-term follow up data exists for complete responders to second line treatments. Here we report long-term outcomes in a cohort of 23 subjects developing SR-GVHD treated with infliximab/daclizumab. A consecutive series of 141 patients with a variety of hematological and non-hematological malignancies as well as nonmalignant hematological disorders including severe aplastic anemia (SAA), paroxysmal nocturnal hemoglobinuria and pure red cells aplasia, underwent a reduced intensity allogeneic HSCT from an HLA identical or single antigen mismatched relative at a single institution between 2/2001 and 12/2008. Transplant conditioning consisted of cyclophosphamide (60 mg/kg days -7, -6) and fludarabine (25 mg/m2days -5 to -1) with or without equine ATG or 6-12 Gy of total body irradiation. GVHD prophylaxis was with cyclosporine with or without additional MMF or MTX. Twenty three patients (median age 35 years, range 13-65 years) developed SR-GVHD at a median of 28 days post transplant. SR-GVHD was defined as absence of response to at least 6 days of high dose methylprednisolone therapy. Following a diagnosis of SR-GVHD, patients received a combination of daclizumab (1mg/kg given on days 1, 4, 8, 15, 22), infliximab (10mg/kg given on days 1, 8, 15, 22), broad spectrum bacterial and anti-fungal prophylaxis, and had their methylprednisolone tapered to 1mg/kg/day. Combined cytokine blockade was highly active against SR-GVHD, with 21/23 (87.5%) patients achieving a complete response (CR), defined as total resolution of GVHD in all involved organ systems. All complete responders survived to hospital discharge. With a median follow-up of 9 years (range 5-10 years), 9/23 (39%) survive, including 6 patients without chronic GVHD whose immunosuppressive therapy (IST) has been discontinued and 3 patients with chronic GVHD (2 limited and 1 extensive) who continue to be tapered off IST. Fourteen of 21 patients with resolution of SR-GVHD died a median 173 days post transplant (range 67-1039 days), including 1 from complications related to recurrent SR-GVHD, 6 from progression of malignancy (all solid tumors), 2 from bleeding related to peptic ulcer disease and 5 from infectious complications including invasive fungal infection and CMV disease. A subgroup analysis showed 5/6 patients with SAA developing SR-GVHD had a complete response to combined infliximab/daclizimab. Remarkably, at a median 6 years follow up, 67% (4/6) of these SAA patients were long-term survivors. All these survivors have maintained normal blood counts and remained transfusion independent with 100% donor chimerism in myeloid and T-cell lineages. Conclusion Patients with SR-GVHD treated with infliximab combined with daclizumab had a high probability of achieving a complete response with nearly 40% of patients having long-term survival. This is the first report to show that long-term survival can be achieved in a substantial proportion of patients receiving combined IL-2 and TNF blockade for SR-GVHD. Disclosures: Off Label Use: Infliximab is FDA approved for the treatment of psoriasis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis and ulcerative colitis. Daclizumab gained FDA approval for use in transplant rejection.

Haematopoietic stem cell transplantation

2015 ◽  
Author(s):  
Drew Provan ◽  
Trevor Baglin ◽  
Inderjeet Dokal ◽  
Johannes de Vos ◽  
Hassan Al-Sader
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Haematopoietic Stem Cell ◽  
Sinusoidal Obstruction Syndrome ◽  
Cell Transplant ◽  
Post Transplant

Haemopoietic stem cell transplantation (SCT) - Indications for haemopoietic SCT - Allogeneic SCT - Autologous STC - Investigations for BMT/PBSCT - Pretransplant investigation of donors - Bone marrow harvesting - Peripheral blood stem cell mobilization and harvesting - Microbiological screening for stem cell cryopreservation - Stem cell transplant conditioning regimens - Infusion of cryopreserved stem cells - Infusion of fresh non-cryopreserved stem cells - Blood product support for SCT - Graft-versus-host disease (GvHD) prophylaxis - Acute GvHD - Chronic GvHD - Veno-occlusive disease (syn. sinusoidal obstruction syndrome) - Invasive fungal infections and antifungal therapy - CMV prophylaxis and treatment - Post-transplant vaccination programme and foreign travel - Longer term effect post-transplant - Treatment of relapse post-allogeneic SCT - Discharge and follow-up

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 </= 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.

A Novel Chemotherapy-Based Allogeneic Hematopoietic Stem Cell Transplant Regimen for Very Young Children with Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3149-3149
Author(s):  
Susan E. Prockop ◽  
Nancy A. Kernan ◽  
Elizabeth G Klein ◽  
Rachel Kobos ◽  
Andromachi Scaradavou ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Young Children ◽  
Cord Blood ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant

Abstract Abstract 3149 Young children in need of allogeneic hematopoietic stem cell transplant (HSCT) are at increased risk of unacceptable side effects from total body irradiation (TBI) and have historically been considered candidates for non-TBI containing regimens. However, disease free survival (DFS) has been poorer in cohorts of very young patients transplanted without TBI and novel chemotherapy based regimens are needed. We report results in a cohort of 14 children all under three years of age at the time of transplant (6 – 32 months; median 19.8 months) using a clofarabine-based ablative regimen. Fourteen patients in this age group have undergone transplant with a regimen consisting of clofarabine 20 mg/m2/day × 5, thiotepa 10 mg/Kg/day × 1 and melphalan 70 mg/m2/day × 2. All patients had high risk disease. Seven (7) pts were transplanted for ALL, 6 for AML and 1 for JMML. Patients with ALL or AML in first remission (CR1) or CR2, were categorized as patients with good risk disease while all other pts were considered as poor risk irrespective of all other factors. Transplant risk was good for 6/7 with ALL, and 3/6 with AML. The patient with JMML had stable disease. Stem cell grafts consisted of unmodified bone marrow (BMT) (N=6), double cord blood (dCBT) (N=7) and T cell depleted PBSCT (N=1). Donors were matched unrelated (N=5) or mismatched unrelated (N=9) including 7 double umbilical cord blood grafts, and one T cell depleted graft. Graft versus host disease (GvHD) prophylaxis was with tacrolimus and methotrexate for unmodified BMT, tacrolimus and mycophenolate for dCBT or T cell depleted HSCT. Two patients died early post transplant of infection (1) and acute GvHD (1). Neutrophil engraftment for the 13 evaluable patients was at a median of 13 days (10 –29 days) for PBSC and BM grafts and 17.5 days (12 –23 days) for recipients of CB grafts. Platelet engraftment for the 12 evaluable patients was at a median of 23 days (16 – 36 days) for recipients of PBSC and BM grafts and 43.5 days (36 –66 days) for recipients of CB grafts. In all five patients developed grade II-IV GvHD, and two patients chronic GvHD. Seven patients developed transaminitis which resolved in all cases. No patients developed Grade IV mucositis. One patient (AML) died after relapsing 5.5 months post transplant. Two patients are alive after relapsing at 1.3 months (AML) and 10.8 months (JMML) post-transplant. Nine of the 14 patients are alive in continuous complete remission seven of whom are greater than 36 months from transplant (40.2 – 71 months). The seven patients without chronic GvHD have had robust immune reconstitution, have responded to vaccination, and continue to meet growth and developmental milestones. Only one patient (transplanted at 14 months of age) has mild neurocognitive deficits. This novel chemotherapy based regimen is associated with durable engraftment of unmodified and cord blood HSCT grafts and promising disease free survival in very young children with leukemia. Based on the low toxicity profile in this cohort of patients higher dosing of clofarabine will be explored as a possible way to improve leukemia remission in the highest risk patients. Disclosures: Off Label Use: Clofarabine.

NCOG-36. LONG-TERM SURVIVAL AND COGNITIVE FUNCTION FOLLOW UP OF PRIMARY CNS LYMPHOMA TREATED WITH R-MVP FOLLOWED BY HIGH DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANT CONSOLIDATION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi159-vi160
Author(s):  
Kate Therkelsen ◽  
Christian Grommes
Keyword(s):  
Stem Cell ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Consolidation Therapy ◽  
Term Survival ◽  
Stem Cell Rescue ◽  
Long Term Follow Up

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a rare central nervous system malignancy, and long-term follow up studies are uncommon. First line therapy is based on high-dose methotrexate and different consolidation therapy options. This is a long-term follow up study of PCNSL patients enrolled in a prospective trial using R-MPV chemotherapy regimen followed by high dose chemotherapy and autologous stem cell rescue to determine long-term survival and cognitive effects. METHODS From June 2005 to September 2011, 32 newly diagnosed immunocompentent PCNSL were enrolled. Patients received 5-7 doses of rituximab (500mg/m2), methotrexate (3.5 gm/m2), procarbazine (100mg/m2), and vincristine (1.4mg/m2) (R-MVP). Consolidation therapy consisted of high dose chemotherapy (HDC) with thiotepa (250 mg/m2), busulfan (3.2 mg/kg), and cyclophosphamide (60 mg/kg), followed by autologous stem cell rescue (ASCT) in those with partial or complete response to R-MVP. Long-term follow-up status including disease status, cognitive status (KPS, NANO score), and leukoencephalopathy (modified Fazkas Scale) were collected. RESULTS 26 of 36 underwent HDC and ACST. Of those, 3 died due to treatment related effects; 2 died of disease progression within two years after ASCT. After a median follow-up of 10.5 years, none of the remaining 21 patients progressed. At the time of last follow up, the median KPS was 90, compared to 80 at time of ASCT. The median NANO score and leukoencephalopathy score post ASCT and at follow-up did not change. Of note, 2 of 4 patients with a partial or complete response to R-MVP that elected not to proceed with HDC-ASCT consolidation, experienced progression at a mean of 52 months. CONCLUSION Long-term follow up demonstrates that treatment was tolerated well with stable leukoencephalopathy on MRI and good performance status. Disease recurrence 2 years after HDC with ASCT consolidation was not observed.

Long Term Results of Non-Myeloablative Stem Cell Transplantation in Non-Hodgkin’s Lymphomas: FLU150/MEL80 (Madrid Protocol).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5047-5047
Author(s):  
Jorge Gayoso ◽  
Pascual Balsalobre ◽  
Jose F. Tomás ◽  
Javier de la Serna ◽  
David Serrano ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Gvhd ◽  
Long Term Results ◽  
Mixed Chimerism ◽  
Cell Transplant ◽  
Mantle Cell ◽  
Heavily Pretreated ◽  
Hodgkin's Lymphomas

Abstract Introduction: Myeloablative allogeneic stem cell transplant has been reserved for long time to young well-fitted patients (pts) due to its high toxicity. Lately, different non-myeloablative (NMA) conditioning regimens have been employed to reduce this toxicity preserving the graft-vs-tumor effect (GVT). Here we present our experience in advanced lymphoma pts. Patients & methods: Since year 2000, we used iv fludarabine 150 mg/m2 days −7 to −4 and iv melphalan 80 mg/m2 day −2 as NMA conditioning for heavily pretreated lymphoma pts, aged >55y or with comorbidities. GVHD prophylaxis consisted in cyclosporine and short course MTX. Stem cells were obtained from peripheral blood of an HLA-identical sibling donor. Gradual cyclosporine tappering from day +50 was initiated if mixed chimerism or persistent disease were present. We evaluated: engraftment rate, toxicities, transplant related mortality (TRM), chimerism kinetics, GVHD incidence and disease free and overall survival (DFS and OS). Results: 18 lymphoma pts (8 follicular, 4 mantle cell, 4 peripheral T and 2 DLBCL) were transplanted since 5/2000 to 1/2007 due to co-morbidities in 4, age>55y in 6 and heavily pretreated pts in 10. Median age was 52y (31–61), 10 were males, median treatment lines were 3 (1–5) including 4 auto-transplanted(22%). After the last treatment, 10 pts were in CR(56%), 4 pts had chemo-sensitive PR(22%) and 4 chemo-resistant disease(22%). Median CD34+/kg infused cells were 5,0 x106(3,7–10,8) and 2,0 x108(0,4–4,4) CD3+ lymphocytes/kg. All pts engrafted, reaching ANC>500 on day +14 (10–20) and platelets>20.000 on day +12 (9–33), except 1 early death. There weren’t any early or late engrafment failures. Early toxicity until day +100 included febrile neutropenia in 6, severe mucositis in 2, hepatic toxicity in 2, VOD in 1, hemorragic cystitis and arrythmia in 1. There were 2 deaths before day +100: 1 refractory congestive heart failure and 1 Pseudomonas’ sepsis(TRM 11,1%) and 2 late deaths beyond +1y due to infections during chronic GVHD treatment. Viral infections were the most prevalent(72%), mainly CMV reactivations (44%) that were relapsing in 17%. There were 7 bacterial infections (4 bacteriemias, 1 meningitis, 1 pneumonia and 1 urinary sepsis). Complete chimerism (CC) was present on day +30 in 38% pts and in 93% pts on day +90. Only 1 pt persisted on mixed chimera until day +180 and 10/10 evaluated pts were on CC after 1 year. Acute grade II-IV GVHD ocurred in 37%, with 25% grade III-IV. Chronic GVHD affected 10/15 pts (67%), limited in 27% and extensive in 40%. Only 1/10 CR pts at transplant relapsed after 95 days and 4/4 pts with chemo-sensitive PR reached CR that persisted after achieving CC on day +90. All chemo-refractory pts died (4/4): 2 early toxic deaths and 2 progressions. Median follow-up was 55 months(28–83) with DFS of 61% and 66,7% OS at 5y. Twelve pts persisted alive in CR with chronic GVHD in 4(33%). Predictors for DFS and/or OS were follicular and mantle cell histology vs others (p<.01), CR or PR at transplant vs refractory (p<.01) and <3 pretreatment lines vs >2 lines (p<.06). Conclusions: After long term follow-up, NMA conditioning with fludarabine and low melphalan dose in advanced lymphoma pts offers good toxicity profile, with high engraftment rate and good disease control if pts were in chemo-sensitive disease pretransplant.

Haematopoietic Stem Cell Transplantation - An Experience from Developing World.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5036-5036
Author(s):  
Khalil Ullah ◽  
Parvez Ahmed ◽  
Shahid Raza ◽  
Tariq Mahmood ◽  
Badshah Khan
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Stem Cell ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Post Transplant ◽  
Transplant Complications

Abstract One hundred and fifty four patients received allogeneic stem cell transplant from HLA matched siblings for various haematological disorders at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from July 2001 to Sep 2006. Indications for transplant included aplastic anaemia (n=66), b-thalassaemia major (n=40), CML (n=33), acute leukaemia (n=8) and misc disorders (n=7). One hundred and twenty patients were male and thirty four were female. Median age of patient cohort was 14 yrs (range 1 ¼ −54 yrs). Pre-transplant infection surveillance was carried out and strict prophylaxis against infection was observed. The mean mononuclear cell dose was 4.2 x 109/kg of recipient. Post transplant complications encountered in our patients were: acute GvHD (grade II-IV) 28.5%, chronic GvHD 15.5%, haemorrhagic cystitis 9.7%, VOD liver 5.1%, acute renal failure 3.2%, bacterial infections 51.2%, fungal infections 15.0%, CMV infection 4%, herpes zoster 4%, tuberculosis 2.6%, pneumocytitis jirovici infection 0.6%, malaria 0.6% patient, graft rejection 5.2% patients and relapse in 4%patients. Certain unexpected rare post transplant complications were also observed in our patients. These included hickman catheter embolization, GB syndrome, deep vein thrombosis, haemorrhagic pericarditis with clots leading to cardiac temponade, idiopathic polycythemia, dengue fever and status epilepticus. Mortality was observed in 27.2% patients. Major causes of mortality were GvHD, VOD, relapse, intracranial haemorrhage, acute renal failure, pseudomonas septicemia, tuberculosis, disseminated aspergillosis and CMV infection. At five years, the overall survival (OS) and disease free survival (DFS) was 72.5% & 70.7% respectively.

Unrelated Donor T-Cell Depleted (TCD) Hematopoietic Stem Cell Transplantation (HSCT) for Patients with Advanced Myelodysplastic Syndromes (MDS): The MSKCC Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1996-1996
Author(s):  
Stephen S. Chung ◽  
Jenna D Goldberg ◽  
Esperanza B. Papadopoulos ◽  
Ann A. Jakubowski ◽  
Sean Devlin ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
High Resolution ◽  
Chronic Gvhd ◽  
Hla Typing ◽  
Refractory Anemia ◽  
Term Survival ◽  
Long Term Survival ◽  
Poor Risk

Abstract Abstract 1996 The outcomes of unrelated HSCT have markedly improved with the advent of high resolution HLA-typing. However, graft-versus host disease (GvHD) remains a limiting factor, particularly in mismatched transplants. Several studies have demonstrated that TCD reduces the incidence of acute and chronic GvHD, potentially allowing for improved outcomes in the mismatched setting. We have observed excellent long term survival in our early experience performing matched related TCD HSCT in patients with advanced MDS, particularly in patients who achieve a complete remission (CR) or second refractory cytopenia phase (RCy2) prior to transplant. We report here our experience performing unrelated TCD HSCT in 85 consecutive patients with advanced MDS. From 1989–2011, 85 patients with advanced MDS (IPSS Intermediate risk [IR]-1 or higher) and AML transformed from MDS underwent TCD HSCT (18 bone marrow [BM], 67 mobilized peripheral blood [PB]) from unrelated donors following conditioning with a total body irradiation-based (25 patients) or a busulfan-based (60 patients) myeloablative regimen. 49 donors were fully matched and 36 were partially matched (9/10 HLA matched: 23; 8/10 HLA matched: 8; 7/10 HLA matched: 1; and 5/6 HLA matched: 4 [before high resolution typing]). The median age was 55 (range 4–73). Prior to conditioning, 80 patients received chemotherapy (28 with a hypomethylating agent, 65 with intensive chemotherapy, and nine with both) and five patients did not receive chemotherapy. Prior to transplant, 34 of the 80 patients who received chemotherapy were in CR, 30 were in RCy2, and 15 failed to achieve remission (10 with RAEB, 5 with AML). Of the five patients who did not receive chemotherapy, two had refractory anemia and three had RAEB. The BM grafts were depleted of T-cells using the soybean agglutinin method followed by sheep RBC rosetting, and the G-CSF mobilized PB stem cell grafts were depleted of T-cells using immunomagnetic CD34+ selection (Isolex initially and CliniMACS after 09/2011). Rejection prophylaxis with ATG was used in all patients. No post-transplant pharmacologic prophylaxis for GvHD was given. 82 of 85 patients engrafted (92%). Three died before engraftment (3.5%, all <28 d after transplant) and two developed late graft failure (2.4%). The day-100 cumulative incidence (CI) of grade II-IV aGVHD was 19% (95% confidence interval [95%CI] 11%-28%), and the 1-year CI of aGvHD, including the late onset form, was 28% (95%CI 18%-38%). When only including grade III-IV aGVHD, the day-100 CI was 9.4% (95%CI 4.3%-17%) and the 1-year CI was 16% (95%CI 9.4%-25%). The 2-year CI of cGVHD was only 3.5% (95%CI 0.9%-9.1%). The overall survival (OS) was 53% (95%CI 43%-63%) at two years and 44% (95%CI 35%-75%) at five years. The relapse free survival (RFS) was 46% (95%CI 36%-57%) at two years and 41% (95%CI 31%-52%) at five years. There was no significant difference in OS/RFS among patients transplanted with fully HLA-matched, 9/10 HLA-matched, or 7–8/10 HLA-matched grafts. There was a trend towards worse OS in patients who had a poor risk (HR) IPSS score at any time prior to transplant; the 2-year OS in this group was 43% (95%CI 32%-60%) versus 64% (95%CI 49%-82%) in the IR-1/IR-2 IPSS groups (p=0.08). Likewise, there was a trend towards worse OS in patients who failed to achieve CR or RCy2 prior to transplant (2-year OS 32% [95%CI 16%-64%]), as compared with patients who achieved CR or RCy2 (2-year OS 58% [95%CI 48%-71%], p=0.25). The overall 1-year CI of relapse was low at 13% (95%CI 7%-21%). The 1-year CI of relapse was significantly higher in patients with IPSS poor risk cytogenetics (27%, 95%CI 5.2%-55%) as compared with intermediate (18%, 95%CI 0.1%-65%) and good (8.4%, 95%CI 0.04%-45%) risk cytogenetics (p=0.03). The 1-year NRM was 36% (95%CI 23%-49%) in those with HR disease and only 18% (95%CI 7%-33%) in those with IR-1/IR-2 risk disease. 5-year OS was superior in transplants done from 2000–2011 (48%, 95%CI 36%-59%) compared with 1989–1999 (25%, 95%CI 6%-50%, p=0.01), reflecting the availability of high resolution HLA-typing and improvements in supportive care. These results indicate that patients with advanced MDS can achieve durable remissions and long term survival after unrelated TCD HSCT with low rates of acute and chronic GVHD even with mismatched donors. Selecting patients for HSCT before progression to IPSS HR disease and induction into CR or RCy2 prior to transplant may maximize the efficacy of this approach. Disclosures: No relevant conflicts of interest to declare.

Long-Term Outcome Of Patients With AL Amyloidosis Treated With High-Dose Melphalan and Stem Cell Transplantation: 19 Year Experience At a Single Center

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3328-3328 ◽  
Author(s):  
Vaishali Sanchorawala ◽  
Gheorghe Doros ◽  
Karen Quillen ◽  
John Mark Sloan ◽  
Anthony C Shelton ◽  
...  
Keyword(s):  
Stem Cell ◽  
Group Performance ◽  
Performance Status ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Term Survival ◽  
Cell Mobilization

Abstract Aggressive treatment of AL amyloidosis with high dose intravenous melphalan followed by autologous stem cell transplant (HDM/SCT) is effective in inducing hematologic and clinical remissions associated with prolonged survival. We have performed 593 transplants from July 1994 to December 2012 in the Amyloidosis Center at Boston Medical Center/Boston University School of Medicine. Patients were enrolled in several sequential institutional review board–approved protocols during the 19-year study period. Eligibility criteria for all protocols required biopsy proof of amyloid disease; evidence of a plasma cell dyscrasia and exclusion of other types as appropriate; at least one major affected organ; and adequate measures of cardiac and pulmonary function, and performance status. Functional measures included cardiac ejection fraction 40% or greater, absence of symptomatic pleural effusions, absence of heart failure or arrhythmias resistant to medical management, oxygen saturation of 95% or greater on room air, lung diffusion capacity of 50% or more of predicted, supine systolic blood pressure of 90 mm Hg or greater, and Southwest Oncology Group performance status score of 2 or less unless limited by peripheral neuropathy. Age, renal function, time from diagnosis, prior therapy, and details of the conditioning regimen varied among the trials. Overall, the median age of patients treated with HDM/SCT was 57 years (range, 28-80). Treatment-related mortality (TRM) defined as death occurring within 100 days after SCT occurred in 51 patients, leading to overall TRM of 9% (n=51/593). Additionally, there were 11 deaths during stem cell mobilization and collection phase. No death has occurred since 2005 during stem cell mobilization and collection and TRM has improved to 5% (n=11/235). Total of 324 patients (55%) received full dose melphalan at 200 mg/m2 and 269 (45%) received modified dose melphalan at 100-140 mg/m2 per protocol, based upon age and organ function. Hematologic CR, as defined by international consensus criteria, occurred in 40% (n=202/508) of evaluable patients measured at 6-12 months post SCT; by intention-to-treat the CR rate was 34%. Hematologic CR occurred in 44% (n=129/291) patients who received 200 mg/m2 of HDM compared to 34% (n=73/217) patients who received 100-140 mg/m2 of HDM (chi square p=0.015). Hematologic relapse occurred in 40 patients (20%) with CR at a median of 3.9 years (range, 1.6-12.4). The median overall survival (OS) is 6.7 years with a median follow-up of 4.5 years. The median OS has not been reached for patients achieving a hematologic CR but exceeds 12.4 years, compared to 5.9 years for those not achieving CR (log-rank p<0.001). The median OS for patients following hematologic relapse is 3.5 years. Twenty-five % of patients are alive, up to 19 years after undergoing HDM/SCT. These data highlight the remarkable long-term survival results that can be obtained in patients with AL amyloidosis treated with HDM/SCT. While survival is strongly dependent upon achieving a hematologic CR, the survival of patients who do not achieve a CR and of those who relapse after CR also is notable, suggesting a benefit of treatment. Strategies to improve risk-stratification of patients and reduce TRM, as well as using sequential or combination therapies to increase the CR rate, will likely improve outcomes in the future for patients who just a few years ago were considered to have a rapidly fatal diagnosis. Disclosures: No relevant conflicts of interest to declare.

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