Incompatibilities of HA-1 and CD62L Polymorphic Adhesion Molecule Induce Graft-versus-Leukemia Effect Rather Than GVHD Resulted in Long-Term Survival in HLA Identical Myeloablative Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1639-1639
Author(s):  
Takamasa Katagiri ◽  
Shintaro Shiobara ◽  
Tatsuo Furukawa ◽  
Jyunichi Tsukada ◽  
Shinji Nakao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Survival Rate ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Acute Gvhd ◽  
Term Survival ◽  
Standard Risk ◽  
Better Than

Abstract Mismatches of minor histocompatibility antigen ( mHag) between HLA identical stem cell donor and host are known as a major risk factor for graft-versus-host disease (GVHD). We determined alleles of 5 polymorphic molecules including HA-1 and 4 adhesion molecules for 107 patients stem cell transplanted from HLA identical donors and investigated the association of their mismatches with relapse rate and GVHD. All of 107 recipients received stem cell transplantation ( SCT) after myeloablative conditioning regimen from 1978 to 2002, 89 received marrow, 15 received PBSC and 3 received both. Stage of the disease at SCT was 63 in standard risk and 43 in high risk. After SCT, 37 developed acute GVHD( ≥2), 50 developed chronic GVHD and 31 relapsed during at least 2 years follow up period. We observed 16.1% of relapse rate in patients with at least one or more incompatibilities and 39.3% of relapse rate without incompatibilities (P= 0.018). Relapse rate of patients with CD62L, HA-1, CD31 at codon 563, CD31 at codon 125 and 49b incompatibilities are as followed 6.1%, 14.3%, 11.7%, 20% and 40% respectively. No difference of acute GVHD was observed in patients with and without incompatibilities. Among standard risk patients, 11 patients with HA-1 incompatibility showed 0% of relapse rate which was better than 45% (P= 0.003) in 47 patients without HA-1 incompatibility. In addition, 10 year survival rate was 100% in the former patients which was better than 52% of survival rate (p=0.03) in the latter patients. These data suggests that polymorphic molecules of HA-1 and CD62L contribute to GVL effect rather than the developing of GVHD which resulted in long term survivor after HLA identical stem cell transplantation. Mhag analysis of donor and host in addition to HLA antigen will help a patient to find a suitable donor in HLA identical family and voluntary donor. Figure Figure

GvATLL Effect in the Relapse and Progression Cases After Hematopoietic Stem Cell Transplantation (HSCT) for Adult T-Cell Leukemia/Lymphoma (ATLL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4299-4299
Author(s):  
Nobuaki Nakano ◽  
Ayumu Kubota ◽  
Mayumi Tokunaga ◽  
Masahito Tokunaga ◽  
Shogo Takeuchi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Skin Lesion ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Poor Responders ◽  
Cell Leukemia ◽  
Term Survival ◽  
Adult T Cell Leukemia

Abstract Abstract 4299 Background Adult T-cell leukemia/lymphoma (ATLL) has a poor prognosis because of its chemo-resistance. Many chemotherapeutic regimens have been created but none of them have shown sufficient results. We proposed allogeneic stem cell transplantation (allo-SCT) for ATLL patients and showed an improved survival rate. However, relapse or progression of ATLL is one of the major limiting factors of survival in post SCT patients. Aims In order to establish a better treatment strategy for poor responders after SCT for ATLL, we analyzed the outcome of relapse or progression cases after allo-SCT. We paid special attention to the graft versus ATLL (GvATLL) effect. Methods There were 37 ATLL patients in which allo-SCT was performed in Imamura Bun-in Hospital (IBH) from June 1998 to April 2009. Twenty-eight cases survived over 100 days after SCT. Sixteen of the 30 patients relapsed. Using data in medical records of IBH, we analyzed transplant characteristics and the outcome of these 17 patients retrospectively. Results Disease status at SCT was CR in 2 patients, 2 PR, 5 SD, and 7 PD. Eight patients received conventional stem cell transplantation (CST) and the other seven patients received reduced-intensity stem cell transplantation (RIST). Fourteen patients in 17 obtained remission (10 CR and 5 PR), but the remaining 2 did not (1 SD and 1 PD) after SCT. The sites of relapse or progression in 17 were skin in 10 patients, 8 peripheral blood, 7 lymph node, 3 central nervous system, and 1 bone. All patients discontinued immunosuppressants after relapse or progression. Eleven patients obtained remission. Especially, in 5 out of 11 patients, remission was obtained only by discontinuation of immunosuppressants (graft-versus-ATLL effect), and the time to remission after discontinuation of immunosuppressants was between 1 to 14 days. Twelve patients were complicated with acute GVHD (grade I-IV). Twelve patients died after SCT. The causes of death were disease progression of ATLL in 5 patients, 3 acute GvHD, 3 infectious complications, and 1 interstitial pneumonia. Four patients who were complicated with acute GvHD survived over 3 years. Discussions Ten patients out of 17 experienced relapse or progression as skin lesion, and 8 patients out of 10 achieved re-remission. It suggests that skin lesion can be a warning sign of ATLL relapse. Since various types of clinical entities, such as ATLL relapse, GvHD, or drug eruption, can manifest as skin lesion after SCT, we strongly recommend to do skin biopsy aggressively to clarify the diagnosis. Ten patients out of 17 achieved re-remission (5 of them achieved only after the discontinuation of immunosuppressant), and 2 patients out of 5 attained long-term survival. This fact raises the possibility that GvATLL effect play a role in controlling exacerbation of ATLL. By focusing on the 5 cases that obtained re-remission only with discontinuation of immunosuppressant, 4 cases showed GvATLL effect prior to GvHD, and one patient experienced fatal grade IV GvHD, respectively. These outcomes suggest that immunosuppressant should be resumed in response to the signs of GvHD deterioration. Relapse/progression cases shows poor survival rate compared with non-relapse ones (60% vs 20% P=0.0028). Although re-remission was highly achieved, this fact suggested that countermeasure against GvHD or re-relapse are indispensable for long-term survival. Summary/conclusions Skin was a major site of relapse or progression after SCT in ATLL patients. A certain number of patients obtained remission only by the discontinuation of immunosuppressants. Four patients survived more than 3 years with their complication of acute GVHD. These results suggest that the GvATLL effect after SCT exists and plays an important role in longer survival for poor responders of post allo-SCT in ATLL patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Long-term outcome after allogeneic stem cell transplantation in multiple myeloma

2021 ◽  
Author(s):  
Sini Luoma ◽  
Raija Silvennoinen ◽  
Auvo Rauhala ◽  
Riitta Niittyvuopio ◽  
Eeva Martelin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
Significant Difference ◽  
Relapse Group

AbstractThe role of allogeneic hematopoietic stem cell transplantation (allo-SCT) in multiple myeloma is controversial. We analyzed the results of 205 patients transplanted in one center during 2000–2017. Transplantation was performed on 75 patients without a previous autologous SCT (upfront-allo), on 74 as tandem transplant (auto-allo), and on 56 patients after relapse. Median overall survival (OS) was 9.9 years for upfront-allo, 11.2 years for auto-allo, and 3.9 years for the relapse group (p = 0.015). Progression-free survival (PFS) was 2.4, 2.4, and 0.9 years, respectively (p < 0.001). Non-relapse mortality at 5 years was 8% overall, with no significant difference between the groups. Post-relapse survival was 4.1 years for upfront-allo and auto-allo, and 2.6 years for the relapse group (p = 0.066). Survival of high-risk patients was reduced. In multivariate analysis, the auto-allo group had improved OS and chronic graft-versus-host disease was advantageous in terms of PFS, OS, and relapse incidence. Late relapses occurred in all groups. Allo-SCT resulted in long-term survival in a small subgroup of patients. Our results indicate that auto-allo-SCT is feasible and could be considered for younger patients in the upfront setting.

Long-term survival in amyotrophic lateral sclerosis after stem cell transplantation into the frontal motor cortex

Cytotherapy ◽  
2016 ◽  
Vol 18 (6) ◽  
pp. 806-808 ◽  
Author(s):  
Héctor R. Martínez ◽  
María Teresa González-Garza ◽  
Jorge Moreno-Cuevas ◽  
César E. Escamilla-Ocañas ◽  
Juan Miguel Tenorio-Pedraza ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Stem Cell ◽  
Motor Cortex ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Term Survival ◽  
Long Term Survival ◽  
Lateral Sclerosis

Durable Remission after Prophylactic Donor Lymphocyte Transfusion Following Allogeneic Stem Cell Transplantation with Reduced Conditioning for High-Risk AML and MDS.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 299-299
Author(s):  
Michael Schleuning ◽  
Christoph Schmid ◽  
Georg Ledderose ◽  
Johanna Tischer ◽  
Meike Humann ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Chronic Infections ◽  
Term Survival

Abstract Prophylactic transfusion of donor lymphocytes (pDLT) is an attractive form of maintenance therapy after allogeneic stem cell transplantation in patients with high risk of relapse. However, clinical experience is limited, and disease response is often achieved at the expense of severe graft-versus-host disease (GvHD). We here report our data on pDLT in high-risk AML and MDS. Cells were given within a prospective protocol that contained a sequence of chemotherapy, reduced intensity conditioning for allogeneic transplantation, and pDLT (FLAMSA-regimen). For pDLT, patients had to be in CR at least 120 days from transplantation, off immunosuppression for 30 days, and free of GvHD. 22/86 patients alive at day +120 fulfilled the criteria for pDLT. They had been transplanted for refractory or relapsed leukemia (n=9 each) or in CR1 because of unfavorable cytogenetics (n=4). 14 patients had an unfavorable karyotype, 8 with complex aberrations. Reasons for withholding pDLT in 64 patients included cGvHD or prolonged immunosuppression (n=38), refractory or relapsed leukemia (n=15), refusal of patient or donor (n=4 each), a history of grade IV acute GvHD (n=2), and chronic infections (n=3). The median time from transplant to first pDLT was 167 days (range 120–297). Median follow up of transfused patients is 696 days (range 209–1341). Ten patients received 1, 6 patients received 2, and 6 patients received 3 transfusions in escalating doses, containing a median of 1x106, 5x106 and 1x107 CD3+ cells/kg at pDLT 1, 2 and 3, respectively. Reasons for giving less than 3 transfusions were GvHD, relapse or refusal of the patient. Induction of GvHD was the main complication; grade III acute GvHD developed in 1, and chronic GvHD in 7 patients. So far, 5 patients have relapsed despite pDLT. One died of refractory leukemia, whereas 2 achieved secondary CR following adoptive immunotherapy. Two patients are currently under treatment. At present, 18/22 patients are alive and in CR at a median of 423 days post DLT. The current leukemia free survival at two years from first pDLT is 79%. Nineteen patients were complete chimeras at time of pDLT. pDLT converted mixed into complete bone marrow chimerism in 1, but failed in 2 cases. In our experience, pDLT is safe after allogeneic transplantation for high risk AML, when given at low doses and to a selected group of patients. Results are encouraging, and long term survival can be achieved. However, further studies need to define more precisely the contribution of pDLT to the therapeutic effect of the entire procedure.

Factors That Contribute to Long-Term Survival In Patients with Leukemia Not In Remission at Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3551-3551
Author(s):  
Hideo Koh ◽  
Hirohisa Nakamae ◽  
Takahiko Nakane ◽  
Masahiro Manabe ◽  
Yoshiki Hayashi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Term Survival ◽  
Long Term Survival ◽  
Kaplan Meier ◽  
Reduced Intensity

Abstract Abstract 3551 Background: Allogeneic hematopoietic cell transplantation (HCT) may even cure leukemia following relapse or primary induction failure. Several pre-transplant variables including age, duration of remission, poor-risk cytogenetics, tumor burden at HCT, type of donor, and performance status reportedly affected the post-HCT prognosis of leukemia that is not in remission. However, there has been insufficient examination of the factors required to achieve long-term survival or cure of leukemia that is not in remission at HCT. We might consider long-term survival without relapse, particularly for more than 5 years, as ‘likely cure' of leukemia. Therefore, we evaluated the factors that contribute to long-term survival (for more than 5 years) in patients with active leukemia at HCT. Method: We retrospectively performed an analysis of leukemia not in remission at HCT performed at our single institute between January 1999 and July 2009. Forty-two patients aged from 15 to 67 years (median age: 39 years) received intensified myeloablative (n=9), myeloablative (n=11) or reduced-intensity conditioning (n=22) for HCT. Twelve patients received individual chemotherapy for cytoreduction within the three weeks before reduced-intensity conditioning for HCT. Diagnoses included de novo AML (n=17), ALL (n=12), CML-AP (n=2), MDS/AML (n=10) and plasma cell leukemia (n=1). In those with acute leukemia, cytogenetic abnormalities were intermediate (n=17, 44%)or poor (n=22, 56%). Seven patients were primarily refractory to induction chemotherapy. The other patients relapsed after conventional chemotherapy or the first HCT. The median number of blast cells in bone marrow (BM) was 26.0% (range; 0.2–100) before the start of chemotherapy for HCT. Six patients had leukemic involvement of the central nerve system. Stem cell sources were related BM (n=3, 7%), related peripheral blood (n=13, 31%) unrelated BM (n=20, 48%) and unrelated cord blood (CB) (n=6, 14%). Thirty-one pairs were matched for HLA-A, B and DRB1 antigens. Three patients were mismatched for one HLA antigen (two at HLA-A, one at HLA-B), and seven were mismatched for two (two at HLA-A and B, five (all CB) at HLA-B and DRB1). The remaining patient was mismatched for all three antigens. Prophylaxis for acute GVHD consisted of calcineurin alone (n=5), calcineurin combined with short-term methotrexate (n=32), calcineurin combined with mycophenolate mofetil (n=2) or none (n=3). In this study, we defined long-term survival as survival without relapse for more than 5 years. Results: Engraftment was achieved in 33 (79%) of 42 patients. Median time to engraftment was 17 days (range: 9–32). Five patients died early after HCT (range 4–20 days). Twenty four (65%) of 37 evaluable patients developed acute GVHD (eight grade I, nine grade II, five grade III, two grade IV), and 12 (50%) of 24 evaluable patients developed chronic GVHD (1 limited, 11 extensive). With a median follow up of 85 months for surviving patients, the five-year Kaplan-Meier estimates of leukemia-free survival rate and overall survival (OS) were 17% and 19%, respectively. At five years, the cumulative probability of non-relapse mortality was 38%. In the univariate analyses of impact of pre-transplant variables on OS, poor-risk cytogenetics, number of BM blasts (>26%), MDS/AML and CB as stem cell source were significantly associated with worse prognosis (p=.03, p=.01, p=.02 and p<.001, respectively). In addition, the five-year Kaplan-Meier estimates of OS in patients with and without cGVHD were 66.7% and 0% (p<.001) respectively. Conclusion: Graft-versus-leukemia effects mediated by cGVHD may have played a crucial role in long-term survival in, or cure of active leukemia. We speculate that effective cytoreduction by individual chemotherapy and/or conditioning for HCT to control disease until cGVHD subsequently occurred might be also important, particularly in leukemia with rapid proliferation. However, intensive conditioning for HCT did not appear to be indispensable in relatively indolent leukemia, even with non-remission status at HCT. In addition, based on our results, CB might be unsuitable as a source of stem cells for leukemia that is active at the time of HCT. Disclosures: No relevant conflicts of interest to declare.

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