Non-Myeloablative Hematopoietic Transplant with Sirolimus Immunosuppression: Determinants of Outcome.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5462-5462
Author(s):  
David F. Claxton ◽  
Chuancai Wang ◽  
Michelle Carraher ◽  
Christopher Ehmann ◽  
Witold Rybka
Keyword(s):  
Graft Failure ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Logit Analysis ◽  
Risk Of Death ◽  
Increased Risk ◽  
Donor Cells ◽  
Alternative Donor ◽  
Disease Free

Abstract We added Sirolimus to an established conditioning regimen in an attempt to optimize engraftment and anti-tumor effects while minimizing GVHD. 55 patients patients with advanced hematological malignancies (median age 60) received cyclophosphamide (1gm/m2 days −7 and −6) and fludarabine (25mg/m2 days −7 through −3) prior to peripheral blood cell (51 patients) or marrow (4 patients) transplant. All received sirolimus with tacrolimus, both adjusted to 5–15ng/ml, and methotrexate (5mg/m2 days 1,3, 6) immunoprophyllaxis. Tacrolimus was tapered from days 30–45 in matched siblings (Msib -12 patients) and days 40–100 in (most) alternative donor recipients (AltD- unrelated donor or 5/6 matched related cells - 43 patients) without acute GVHD. Median follow-up is 313 days in AltD patients and 337 days for Msib patients. All Msib cells engrafted, whereas 3/43 AltD recipients showed primary graft failure or secondary graft failure (1/43). Msib recipients engrafted more rapidly than those with AltD transplants (p<0.01). For AltD recipients, the CD34 dose had a positive significant effect on donor engraftment - chimerism (p<0.05 for all points up to D100). Median overall and disease free survival was 287 and 230 days respectively for AltD patients and 303 and 167 days for Msib recipients. Amongst AltD patients, 17/43 survive progression free at D114-1167 (median D416), while in MSib patients only 1/12 survives progression free (p=0.0023 ). Two additional patients are disease free after donor lymphocytes (DLI) or withdrawal of immunosuppression in each group. No patient in the Msib group had transplant related mortality (TRM), but in the AltD group there were nine TRMs, including 7 from GVHD (NS). Multivariate analysis showed CD34 dose and donor types had no significant effect on development of progressive disease (PD). However, in general the odds ratio of any PD decreased exponentially as the level of chimerism increased. For example, at D100 the odds of developing PD decreased by 0.699 times when the level of chimerism increased by 0.1. Multinomial logit analysis showed that compared to GVHD death, the odds ratios for PD death decreased exponentially as the level of chimerism increased. In this series of patients with advanced hematological malignancy, Alternative donor cells provided a higher probability of control of disease, albeit with a trend to higher TRM. Higher CD34 cell doses were associated with improved donor engraftment (chimerism) in AltD recipients. For AltD recipients, risk of PD was reduced by increasing donor chimerism, but increasing chimerism is associated with increased risk of death from GVHD. Efforts to improve control of malignancy via more rapid engraftment of donor cells must be tempered with concern regarding potentially severe GVHD. Figure Figure

Allogeneic Stem Cell Transplantation (SCT) in Untreated First Relapse or Following Re-Induction Chemotherapy for Patients with Acute Myeloid Leukemia (AML).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5143-5143
Author(s):  
Rachanid Pornvipavee ◽  
Walter K. Kremers ◽  
Rachel A. Pedersen ◽  
Michelle Elliott ◽  
William J. Hogan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Induction Chemotherapy ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Multivariate Model ◽  
Lower Percentage ◽  
Risk Of Death ◽  
Increased Risk ◽  
Blast Cells ◽  
First Relapse

Abstract Background The timing of SCT for treatment of AML after first relapse is controversial, i.e.,whether to proceed to SCT at the time of relapse or to proceed to chemotherapy re-induction first in an attempt to reach a second remission. The purpose of this study is to determine the optimal time of allogeneic SCT in AML patients in first relapse by comparing outcomes of allogeneic SCT between patients untreated and patients post re-induction chemotherapy. Method This retrospective study was approved by the Mayo Foundation IRB. Between February 1983 and March 2003, 60 patients with AML in untreated first relapse (REL1) or post re-induction chemotherapy (CT) underwent allogeneic SCT in Mayo Clinic, Rochester. Study outcome included overall survival (OS), disease free survival (DFS), and transplant related mortality (TRM). The outcome was compared between the patients who underwent allogeneic SCT at REL1 and CT. Survival was analyzed using Kaplan-Meier (KM) and groups were compared statistically with the log-rank test. Result Of the 60 patients receiving allogeneic SCT , 25 patients and 35 patients underwent SCT at REL1 and CT, respectively. In the group of CT, 23 patients (66%) achieved CR2 while 12 patients (34%) had refractory disease. Forty-nine of 60 patients received cyclophosphamide and total body irradiation (Cy/TBI) as a conditioning regimen and the remainder received busulfan and cyclophosphamide( Bu/Cy). Patients in REL1 were older at SCT (median age 38 vs 31 years p= 0.024 ) and had lower percentage blast cells in bone marrow at first relapse (median 15% vs 50% p=0.00095) than in CT group. Difference in other baseline characteristics were not significant. KM analysis showed that the two groups did not show statistically differences in OS (p=0.43), DFS (p=0.68), and TRM (p=0.25). However, there were trends toward longer median OS (26.2 vs 5.4 months) and DFS (11.9 vs 3.3 months) with REL1 versus CT. OS at 1 year was 56 % for REL1 and 34.3 % for CT and at 5 year 32.1 % and 28.6 %, respectively. DFS at 1 year was 48 % for REL1 and 31.4 % for CT and at 5 years 22.9 % and 24.5 % respectively. TRM at 1 year was 25% for REL1 and 40 % for CT. A univariate Cox Proportional Hazard analysis for survival showed that unfavorable cytogenetics at diagnosis and relapse, antecedent MDS, and shorter duration of CR1 were significantly associated with a higher risk of death. Higher percentage of blast cells in bone marrow at first relapse was not significantly associated with a higher risk of death. In a multivariate model, unfavorable cytogenetics at first relapse and shorter duration of CR1 were both significantly associated with an increased risk of death. In this study, even after adjusting for other factors in a multivariate model, the difference between REL1 and CT groups was not statistically significant. Conclusion This study suggests that outcome of allogeneic SCT was comparable between REL1 and CT. Patients with AML in first relapse may proceed to allogeneic SCT because there appear to be no statistical differences in REL1 versus re-induction chemotherapy before SCT. REL1 patients tended to have a better outcome than CT patients.

Second Allogeneic Bone Marrow Transplantation for Patients with Either Graft Failure or Relapsed Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1770-1770
Author(s):  
Stella Santarone ◽  
Erminia Di Bartolomeo ◽  
Pasqua Bavaro ◽  
Paolo Di Carlo ◽  
Paola Olioso ◽  
...  
Keyword(s):  
Graft Failure ◽  
Malignant Disease ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Disease Free ◽  
Median Interval

Abstract Despite myeloablative and immunosuppressive conditioning therapy, allogeneic bone marrow transplantation (BMT) may fail because of either graft failure or relapse of the malignant disease. In this study we have evaluated the impact of second BMT on long-term disease-free survival (DFS) in 42 patients who were transplanted in our institution between January 1983 and March 2005. GRAFT FAILURE. Eleven patients (4 with aplastic anemia, 4 thalassemia major (TM), 3 chronic myeloid leukemia (CML), 2 acute myeloid leukemia (AML), 1 acute lymphoblastic leukemia (ALL), 1 myelodisplastic syndrome (MDS) received a second BMT for graft failure, either primary (n=8) or secondary (n=3). The median age at time of first BMT was 19 years (range, 3 to 42). The median interval between the first and second BMT was 35 days (range, 27 to 532). Donors were the same of the first BMT. They were HLA genotipically identical (n=8) or HLA phenotipically identical (n=1) or 1 antigen mismatched family members. Four patients died for BMT related causes (2 for acute GvHD, 1 for heart failure and 1 for CNS hemorrhage and rejection). Six patients are now living after a median follow-up of 169 months (range, 52 to 202). Five patients are cured and one had an autologous thalassemia reconstitution and is now living under transfusion treatment. RELAPSE. Thirty-one patients (11 with CML, 9 AML, 9 ALL, 1 MDS, 1 TM) were given a second BMT following relapse of the malignant disease. The median age at time of first BMT was 27 years (range, 1 to 43). The median interval between the first and second BMT was 528 days (range, 115 to 5584 ). Thirty patients received the second BMT from the same HLA genotipically identical family member used for the first transplant. One patient was given the first BMT from a matched unrelated donor and the second transplant from an haploidentical brother. The 6 months transplant related mortality (TRM) was 19%. Six patients died for BMT related causes (4 for acute GvHD, 1 for heart failure and 1 for infection and multiorgan failure). Eight patients had leukaemia relapse following second BMT. Five of them died of chemotherapy complications. One of them, who was reinducted into complete remission and received a third BMT from an unrelated donor, died because encephalopathy. Nineteen patients are living after a median follow-up of 72 months (range, 4 to 236). The 5-years probabilities of overall survival and disease free survival (DFS) were 59% and 52% respectively. The 5-years DFS for AML, CML and ALL patients was 72%, 54% and 12% respectively (p=0.03). The 5-years DFS for 17 patients conditioned with TBI and for 13 patients conditioned with busulphan (BU) was 62% and 31% respectively (p=0.09). This study show that many patients may benefit from a second BMT either following graft failure or leukemia relapse with an acceptable TRM. In particular, patients with AML or CML are the best candidates to be cured from second BMT. TBI conditioning regimen gives better results as compared to BU regimen.

One Antigen HLA-Mismatched Related and 8/8 Allele Matched Unrelated Donors Are Associated with Similar Survival after Hematopoietic Cell Transplantation for Acute Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 965-965
Author(s):  
David Valcarcel ◽  
Fangyu Kan ◽  
Tao Wang ◽  
Stephanie J. Lee ◽  
Stephen R Spellman ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Free Survival ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Related Donor ◽  
Disease Free

Abstract Patients in need of an allogenetic hematopoietic cell transplant but who lack an HLA genotypically identical sibling donor, are faced with the decision to consider a single HLA antigen mismatched related donor, or a search for a suitable 8/8 matched unrelated donor. We compared the outcomes of adult patients (≥18 years old) receiving a transplant for the treatment of AML or ALL in first or second remission from either a one-antigen mismatched related donor (MMRD group, N=89) reported to the CIBMTR or an 8/8 HLA-A, B, C and DRB1 allele matched unrelated donor (UD group, N=700) facilitated by the NMDP between 1995–2005. MMRD group was typed by serological or DNA-based methods for HLA-A, -B and –DR with all results verified by lab report review. The UD group was retrospectively typed for HLA-A, B, C and DRB1 by high resolution typing methods. Most received myeloablative conditioning regimens (77%), calcineurin inhibitor-based GVHD prophylaxis (100%) and T cell replete grafts (100%). 13% received ATG with the conditioning regimen. Median follow-up was 54 and 38 months in the MMRD and UD groups, respectively. The MMRD group was younger (median age 35 vs 43, p=0.002), had more ALL patients with low-risk cytogenetics (43% vs 18%, p=0.005), had older donors (median age: 38 vs 34, p=0.047), were more likely to receive methotrexate for GVHD prophylaxis (89% vs 77%, p=0.014) and were more likely to be transplanted prior to 2001 (62% vs 24%; p<0.001). There were no differences in patient or donor gender, diagnosis, disease-status, cytogenetic-risk of AML, time from diagnosis to transplant, stem cell source, conditioning regimen, use of ATG and Karnofsky index. Univariate comparisons (MMRD vs. UD) showed: 3-year OS (42% vs 44%, p=0.647), 3-year DFS (41% vs 41%, p=0.931), 3-year TRM (39% vs 31%, p=0.136), 3-year incidence of relapse (20% vs 28%, p=0.094), grade III–IV acute GVHD by 100 days (22% vs. 15%, p=0.147), chronic GVHD by 1 year (35% vs 47%, p=0.029). All multivariate analyses were adjusted for patient and transplant characteristics and are shown in the table below. In summary, transplants utilizing one-antigen mismatched related and 8/8 allele-matched unrelated donors did not significantly differ in overall survival or disease free survival, but chronic GVHD was more frequent after UD transplantation. Outcome RR (MMRD vs. UD) 95% CI p-value Survival 0.99 0.73–1.34 0.94 Disease-free survival 1.06 0.80–1.41 0.69 Treatment related mortality 1.14 0.77–1.69 0.52 Relapse 0.81 0.50–1.30 0.38 Acute GVHD III–IV 1.53 0.91–2.57 0.11 Chronic GVHD 0.58 0.39–0.85 0.006

The Role of Hematopoietic Cell Transplantation (HCT) for Burkitt Lymphoma: a Report From the Center for International Blood and Marrow Transplant Research (CIBMTR)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2390-2390
Author(s):  
James L. Gajewski ◽  
Jeanette Carreras ◽  
Hillard M. Lazarus ◽  
Ginna G. Laport ◽  
Silvia Montoto ◽  
...  
Keyword(s):  
Burkitt Lymphoma ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Unrelated Donor ◽  
Free Survival ◽  
Disease Free

Abstract Abstract 2390 Burkitt lymphoma (BL) is an aggressive B cell lymphoma primarily affecting children and young adults and is characterized by the highest doubling time of any tumor. Cyclical intensive chemotherapy and rituximab confer high complete remission (CR) rates and 80% long term disease free survival in chemotherapy sensitive disease. The role of autologous (autoHCT) or allogeneic (alloHCT) transplant is not well described in BL. We report the outcomes of 241 recipients of HCT for BL between 1985 and 2007 reported to the CIBMTR. Five patients (pts) received syngeneic twin grafts in addition to autoHCT in 113 pts, HLA identical sibling alloHCT (SIB) in 80 pts and mismatched related or unrelated donor (UNR/MM) alloHCT in 48 pts. Baseline patient and disease related risk factors varied significantly between cohorts (table1). The autoHCT cohort had a higher proportion of pts with chemotherapy sensitive disease (86%), peripheral blood grafts (73%) and HCT in first CR (42%). In the UNR/MM cohort, 25% pts were chemotherapy resistant and only 6% were in CR1. The use of autoHCT has declined in recent years with the majority (81%) performed before 2001. Conditioning regimen for alloHCT was myeloablative in 88% (86% and 92% in SIB and UNR/MM respectively). Treatment related mortality (TRM) was higher in alloHCT recipients (table1). Cumulative incidence of relapse/progression at 5 yrs (95% CI) was 44 (35-53)% for autoHCT, 42(31-53)% for SIB and 48 (34-62)% for UNR/MM. For autoHCT, 5-yr progression free survival (PFS) was 48(39-58)%, 78% for those in first CR versus 27% for disease beyond CR1 (p<0.001). For alloHCT, 5-yr PFS was 50% for those in first CR versus 19% for disease beyond CR1 (p=0.001) (figure 1). 5-yr PFS was 30 (20-41)% for SIB and 22 (12-35)% for UNR/MM. Progressive BL was the commonest cause of death. Conclusion: While autoHCT and alloHCT are both feasible in patients with BL, the use of autoHCT appears to be declining in recent years concomitant with the advent of modern chemotherapy. AlloHCT was performed in those with considerably higher risk disease. Approximately one fifth of advanced BL pts receiving alloHCT beyond CR1 had long term disease free survival. Disclosures: No relevant conflicts of interest to declare.

Extent of lymphadenectomy (LA) and outcome for patients with stage I non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7604-7604
Author(s):  
M. M. DeCamp ◽  
A. Recht ◽  
M. Nikolov ◽  
J. C. Flickinger ◽  
J. M. Varlotto
Keyword(s):  
Disease Free Survival ◽  
Stage I ◽  
Maximum Difference ◽  
Free Survival ◽  
Risk Of Death ◽  
Increased Risk ◽  
Staging Accuracy ◽  
Seer Data ◽  
Minimum Number ◽  
Disease Free

7604 Background: It is uncertain if LA affects overall survival (OS) or disease-free survival (DFS) rates for patients with stage I NSCLC and, if performed, what is the minimum number of nodes that should be recovered. Methods: 24,273 patients with stage I NSCLC diagnosed from 1992–2002 underwent a definitive surgical procedure and were included in the SEER data-base. For patients diagnosed from 1998–2002, outcome was examined separately for patients having only N1 (2,683 patients) or N2 nodal (1,019 patients) dissections. Results: For the entire population, LA was associated with an increase in the 5-year OS rate from 41.7% to 58.4% (p <0.0001) and in DFS from 58.4% to 72.9%, compared to not having LA. For patients undergoing only N1 dissection, LA was also associated with significant improvements in OS and DFS, compared to no LA (p=0.056 and 0.043). The maximum difference between those with no LA and those with only N1 dissection was when 11–16 nodes were removed (4-year OS, 40.0% vs. 68.2%; DFS, 40.0% vs. 60.4%). For patients undergoing only N2 dissection, LA was associated with a significant improvement in OS (p=0.045) and a trend for a DFS benefit (p=0.086), with the maximum difference between those with no LA and those with 7–10 nodes removed (4-year OS, 75.0% vs. 77.7%; DFS, 75.0% vs. 85.0%). Those patients undergoing removal of ≥ 11 N2 nodes were found to have a significantly increased risk of death to cardiopulmonary/infectious causes (5.56% vs 1.79%) as compared to those patients having < 11 nodes removed (p = 0.023). Conclusions: LA was associated with increased rates of OS and DFS, compared to no LA. Our results also suggest the minimum number of recovered nodes needed to see the maximum staging accuracy of LA. No significant financial relationships to disclose.

Unrelated Donor Bone Marrow Transplants in Children

1994 ◽  
Vol 3 (5) ◽  
pp. 413-420 ◽  
Author(s):  
Alfred Grovas ◽  
Stephen A. Feig ◽  
Sheryl O'rourke ◽  
Leonard Valentino ◽  
Fran Wiley ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Marrow Transplant ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Short Course ◽  
Increased Risk ◽  
Disease Free

Only a small proportion of children who might benefit from bone marrow transplant (BMT) have an HLA-identical sibling. To provide this potentially curative therapy to patients without a matched related donor, marrow transplants using less well matched related donors or unrelated donors (identified through computerized donor registries) have been performed. We report the outcome of 24 consecutive unrelated donor BMT's performed on children. Eligible diagnosis included acute leukemia (AL) (n = 15), chronic myelogenous leukemia (CML) (n = 4), myelodysplastic syndrome (MDS) (n = 3), and severe aplastic anemia (SAA) (n = 2). All donor/recipient pairs were sero-matched at 5 or 6 of the 6 HLA A, B, and DR antigens. Several different preparative regimens were used, but fractionated total body irradiation (TBI) was used in 20 patients. All recipients received graft-versus-host-disease (GVHD) prophylaxis with cyclosporine-A (CSA), four with short course methotrexate (MTX), 14 in combination with short course MTX and methylprednisolone (MPS), and five in combination with a mouse monoclonal antibody to CD5, coupled to the A-chain of ricin (Xomazyme-65). One patient received CSA and MPS alone after a T-cell depleted marrow transplant. Twenty of 23 evaluable recipients engrafted (87%). Two patients with CML never engrafted and had autologous marrow recovery, one patient with SAA died at 128 days without evidence of engraftment, and there was one early death at day + 9. Fourteen of 20 patients (70%) with stable donor-derived hematopoiesis developed significant acute GVHD ≥ grade II). Eleven of 15 engrafted patients who survived > 100 days after BMT developed chronic GVHD (73%). Thirteen patients survive, 10 disease-free; 2 yr actuarial survival and disease-free survival are 47% and 41%, respectively. Of the 19 engrafted patients with leukemia or MDS, only three have relapsed. The actuarial relapse risk at 2 yr is 24%. Unrelated donor transplants in children are associated with an increased risk of GVHD and nonengraftment compared to matched sibling transplants. Increased donor age is significantly associated with a greater risk of acute GVHD.

Allogeneic and Matched Unrelated Donor Hematopoietic Stem Cell Transplantation (HSCT) for Hematologic Malignancies Using a Modified Reduced Intensity Conditioning Regimen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5324-5324
Author(s):  
Marion Raflores ◽  
James Rossetti ◽  
John Lister ◽  
Richard Shadduck ◽  
John Lech ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Reduced Intensity Conditioning Regimen ◽  
Disease Free ◽  
Related Mortality

Abstract INTRODUCTION:Use of a reduced intensity conditioning regimen (RICR) in hematopoietic stem cell transplant may result in lower treatment related mortality (TRM), less acute graft versus host disease (aGVHD) and better survivability, utilizing the graft versus tumor effect from HSCT. METHODS: Our institution’s original RICR protocol conditioning regimen (Trial A) consists of fludarabine 30 mg/m2 (Day-5 to D-2), melphalan 140–180 mg/m2 (Day -3) and ethyol 910 mg/m2 (Day-3) in addition to mycophenolate mofetil 1 g q12H and tacrolimus(serum level 5–15 ng/ml) beginning Day -3 as immunosuppressive therapy. Transplantation was done using peripheral blood stem cells from the best HLA-antigen match sibling (allo) or matched unrelated donor (MUD). We retrospectively compared transplant data from this original protocol to a modified RICR protocol (Trial B) using a lower dose of melphalan 100mg/m2 and addition of thymoglobulin 2mg/kg/d (D-2 to D0). RESULTS: 46 patients were transplanted in Trial A with median age of 46 years. 25 patients had allogeneic and 21 had MUD transplant. 30 patients were transplanted in Trial B with median age of 44 years. 22 patients had an allogeneic and 8 had a MUD transplant. All patients were heavily pretreated with 13 patients in Trial A and 9 patients in Trial B have undergone at least one previous stem cell transplant. At D30, all patients in Trial B were alive while 11% of patients in Trial A died of treatment related cause. At D100, 51% of patients in Trial A and 70% of patients in Trial B were alive. D100 TRM was 40% in Trial A and 20% in Trial B. Table 1. Treatment Outcome OS(%) TRM (%) RM (%) Trial A Trial B Trial A Trial B Trial A Trial B OS:overall survival TRM:treatment related mortality RM: relapse mortality 30 Days MUD 81 100 19 0 0 0 Allo 96 100 4 0 0 0 Total 89 100 11 0 0 0 100 days MUD 40 63 60 38 0 0 Allo 60 73 24 14 16 14 Total 51 70 40 20 9 10 1 year overall survival was 30% in trial A and 20% in Trial B. 1 year disease free survival (DFS) was 18% in trial A and 13% in Trial B. Table 2. 1 year treatment outcome* Overall Survival(%) Disease Free Survival (DFS) % Trial A Trial B Trial A Trial B *for Trial B, 5 living patients have not yet reached 1 year follow-up MUD 21 13 14 0 Allo 37 23 21 18 Total 30 20 18 13 Incidence of aGVHD≥2 in patients not receiving DLI and alive for more than 30 days post transplant was 56% in Trial A (MUD 67%, Allo50%) and 25% in Trial B (MUD63%, Allo 6%). At D100, aGVHD was the most common cause of death in Trial A while overwhelming sepsis was leading cause of death in Trial B. WBC engraftment with ANC&gt;500 was achieved in 98% of patients in Trial A and 93% of patients in Trial B. Average day of engraftment was 13 days in Trial A and 15 days in Trial B. Platelet engraftment with platelet count at least 20,000 was achieved in 80% of patients in both protocols with average day of engraftment at 18 days in Trial A and 21 days in Trial B. 95% of patients in Trial A had achieved at least 80% donor marrow cells at D100 while only 81% achieved this level of chimerism in Trial B. CONCLUSION: The modified RICR protocol for HSCT is a tolerable regimen which results in a lower incidence of D100 TRM and aGVHD but overall and disease free survival are not improved. Marrow engraftment is achieved although slightly delayed compared to the original protocol.

Allogeneic Stem Cell Transplantation With Reduced Intensity Conditioning Regimen In Patients With Relapsed Hodgkin´s Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5511-5511
Author(s):  
Maria Marta Rivas ◽  
Mariano Berro ◽  
Sebastian Yantorno ◽  
Maria Virginia Prates ◽  
Jorge H Milone ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Abstract Introduction Hodgkin´s Lymphoma (HL) is a highly curable disease. However, there are still patients with primary refractory disease or who relapse after first-line treatment, or even after high-dose chemotherapy with hematopoietic cell rescue. Allogeneic stem cell transplant (ASCT) is therapeutic for this patients. Objective To analyze the experience with relapsed HL patients that received ASCT with reduced intensity conditioning (RIC)regimen in 8 Argentine Medical Centers. Design and Population We performed a retrospective multicenter analysis from data obtained from medical records. Fifty-four patients with relapsed HL who received ASCT had a median age of 26years. The relationship between male / female was 1/1. Only 3 patients (5.5%) at the time of transplant had a performance status> 1 according to ECOG. Ninety-six percent of the patients had received previously autologous transplant. Most patients 43 (80%) received an identical sibling donor transplant. All patients receiving unrelated donor transplants had in vivo lymphocyte depletion as prophylaxis of graft versus host disease. Forty-three patients (79.6%) received as a conditioning regimen Fludarabine + Melphalan. The disease status at transplant was: complete remission (CR) 33%, partial remission (PR) 54%, stable disease / progressed (SD / PD) 13%. Results With a median follow up of 2.7 years, actuarial overall survival (OS) at 1 and 5 years was 65% and 20% respectively and disease free survival (DFS) at 1 and 5 years was 35 % and 18% respectively. The incidence of acute GVHD grade II-IV was 31%. Patients in CR at the time of transplant showed significant differences compared with those who were not in CR in DFS (1-5 years 52-27% vs 19-14%, p=0.01), OS (1-5 years 76-38% vs 59-13%, p=0.02) and non relapsed mortality (NRM) (1-5 years 6-12% vs 34-39%, p=0.04). Age, PS, the use Fludarabine + Melphalan as conditioning regimen, unrelated donor, aGVHD, were not variables that modified the overall survival and disease-free survival. Conclusion The ASCT with RIC regimen is a feasible therapeutic option in patients with HL, especially in patients who can achieve CR. The low rate of DFS is still an issue in this setting, may be new drugs may help in optimizing pretransplant response status to improve patients’ outcome. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Graft Failure in Patients With Hematological Malignancies: A Successful Salvage With a Second Transplantation From a Different Haploidentical Donor

2021 ◽  
Vol 8 ◽  
Author(s):  
Yu-Qian Sun ◽  
Yu Wang ◽  
Feng-Rong Wang ◽  
Chen-Hua Yan ◽  
Yi-Fei Cheng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Graft Failure ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Mixed Chimerism ◽  
Unrelated Donor ◽  
Second Transplantation ◽  
Neutrophil Engraftment

Graft failure (GF) is a fatal complication of allogeneic stem cell transplantation, especially after haploidentical transplantation. The mortality of GF is nearly 100% without an effective salvage method. A second transplantation is usually necessary to save the patient's life. However, there is no standardized regimen, and the outcome is usually disappointing. We report on a prospective single-center study using a reduced-intensity conditioning regimen with different haploidentical donors (HIDs). Patients with GF after the first transplantation were enrolled in a prospective single-arm clinical trial (ClinicalTrials.Gov ID: NCT03717545) at the Peking University Institute of Hematology. The conditioning regimen consisted of fludarabine (30 mg/m2) (days−6 to−2) and cyclophosphamide (1,000 mg/m2/day) (days−5 to−4). Patients underwent a second transplant from a different HID using a granulocyte colony-stimulating factor primed bone marrow and peripheral blood stem cells. The primary outcome was neutrophil engraftment at day 28. The secondary outcomes included platelet engraftment at day 100, transplant-related mortality (TRM) at day 30, TRM at day 100, and overall survival (OS) at 1 year. From March 2018 to June 2020, 13 patients were enrolled in this clinical trial. Of the 13 patients, five had acute myeloid leukemia, five had acute lymphoblastic leukemia, two had myelodysplastic syndromes, and one had a non-Hodgkin lymphoma. The median age at first transplantation was 38 years (range, 8–55 years). As for the first transplantation, 11 patients underwent haploidentical transplantations and two underwent unrelated donor transplantations. At the time of GF, three patients had complete donor chimerism, five had mixed chimerism, and five had complete recipient chimerism. The median time from the first transplantation to the second transplantation was 49 (range 35–120) days. The medians of infused cell doses were as follows: mononuclear cells 7.93 (5.95–12.51) × 108/kg and CD34 + cells 2.28 (0.75–5.57) × 106/kg. All 13 patients achieved neutrophil engraftment after the second transplantation, with a median engraftment time of 11 (range 10–20) days after transplantation. The platelet engraftment rate on day 100 after transplantation was 76.9%. The TRMs at day 30, day 100, and 1-year were 0, 0, and 23.1%, respectively. The OS and disease-free survival at 1-year were 56.6 and 48.4%, respectively. For patients with GF after first transplantation, a second transplantation using a fludarabine/cyclophosphamide regimen from a different HID was a promising salvage option. Further investigation is needed to confirm the suitability of this method.

Are Back-Up Bone Marrow Harvests of Value in Unrelated Donor Allogeneic Transplants?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5023-5023
Author(s):  
Christy Stotler ◽  
Edward Copelan ◽  
Ronald Sobecks ◽  
Lisa Rybicki ◽  
Robert Dean ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Graft Failure ◽  
Clinical Status ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
The Other ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Allogeneic Transplant

Abstract In June 2007 four members of the University of Michigan Cardiothoracic transplant team died in a plane crash while transporting organs to an expectant transplant recipient. Matched Unrelated Donor Stem Cell transplants (MUDs) require that patients receive the preparative regimen before the hematopoeitic stem cells are transported. Our transplant program performs a “back-up” autologous harvest prior to administration of the conditioning regimen for use if the donor graft fails to arrive or if graft failure occurs. However, this practice is not uniform and insurers sometimes balk at payment. To evaluate the value of their routine collection, we reviewed the results of our center’s use of back-up marrows. 215 MUD transplants were performed at CCF from 1/95 to 12/05 and 146 recipients underwent back-up marrow collection. All recipients of adult MUD or Cord Blood transplants with hematologic malignancies in complete remission were harvested. Of 146 back-up marrows harvested, 15 patients (10%) had their back-up harvest infused. All 15 patients received their rescue marrow infusion for graft failure (adult MUD, n=12; Cord, n=3) 0.7–7.6 (median 1.1) months after the original transplant. Seven of the 15 (46%) patients had undergone full molecular matching, the other 8 (54%) patients being matched by serology for class I antigens and DNA typing for class II antigens. 9 patients were 6/6 serologic or molecular matches, 3 patients were 5/6 matches, and the 3 cord transplants were 4–5/6 matches. Deteriorating clinical status and a need for rapid engraftment was the rationale for infusion of autologous back-up marrow, as opposed to seeking additional donor cells (which potentially takes several weeks). Five patients (33%) are alive and in complete remission 14.6 to 137 (median 91) months from back-up infusion. Of these, two were bridged to a second MUD transplant. These two patients are alive and well at days 4200 and 1950 respectively. The other three have shown surprisingly durable disease free survival without repeat allogeneic transplant. Survivors Following Rescue Autologous Stem Cell Infusion Patient No. Primary Disease Transplant Material - all MUD Day of rescue infusion HLA typing of 1st transplant Second transplant Outcome 1 CML BM +29 Serologic 6/6 Yes (+560) Alive last f/u (+4200) 2 CML BM +33 Serologic 5/6 No Alive last f/u (+3363) 3 NHL BM +62 Serologic 8/8 No Alive last f/u (+2833) 4 AML Adult PBSC +230 Molecular 8/8 Yes (+1581) Alive and well (+1950) 5 AML Cord +38 Molecular 5/6 No Alive last f/u (+482) In total, 5 patients went on to a second transplant, all from adult MUD donors. Three patients died following second transplant - two from relapse and the 3rd from ARDS. Ten patients died following back-up infusion: 4 (36%) from relapse, 5 (54%) from infections and 1 from graft failure before rescue cells could engraft. Within this group, patients lived a mean of 114.5 (4–357) days from autologous rescue. Five patients were discharged from the hospital and lived a mean of 7.1 (1–12) months from discharge. In conclusion, a rescue autograft following graft failure may allow for rapid hematopoeitic recovery providing an opportunity for a second allogeneic transplant if another donor is available. In some cases it can directly result in durable remission. This procedure has saved the lives of 5 patients and should be more widely employed.

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