Non-Myeloablative vs. Conventional Allogeneic Hematopoietic Stem Cell Transplantation for Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1132-1132
Author(s):  
Brad Pohlman ◽  
Tao Jin ◽  
Elizabeth Kuczkowski ◽  
Stacey Brown ◽  
Ronald Sobecks ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
High Dose ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem

Abstract Non-myeloablative allogeneic stem cell transplantation (NMT) is increasingly used as an alternative to conventional bone marrow transplantation (BMT). Limited NMT data is available for lymphoma patients (pts). Most series include all hematological malignancies and only a minority with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL). Therefore, we reviewed the Cleveland Clinic BMT Program experience with lymphoma pts and specifically compared the outcome between NMT and BMT. Between July 2, 1985 and December 7, 2004, 67 pts received a matched related (n=47) or unrelated (n=20) donor BMT (n=46) or NMT (n=21) for HL (n=11), aggressive NHL (n=32), indolent NHL (n=23), or unknown NHL (n=1). Pts with lymphoblastic, Burkitt, or atypical Burkitt-like lymphoma were excluded. Compared to BMT pts, NMT pts were older, had longer time from diagnosis to transplant (tx), and were more likely to have a normal LDH and be in remission (CR/PR) at tx. The median follow-up of surviving BMT and NMT pts was 73.8 (range 11.8–106.7) and 20.6 (range 2.8–44.0) months, respectively. 18 (39%) BMT and 5 (24%) NMT pts progressed, and 9 (20%) BMT and 2 (10%) NMT pts died from lymphoma. The incidence of grade 2–4 acute GVHD was not different between the BMT and NMT groups. Among all pts, the risk of lymphoma progression was significantly higher in pts with compared to pts without GVHD (Figure 1). The overall survival for NMT pts was significantly better than for BMT pts (P=.019). Among 15 pts that previously received high dose therapy with autologous stem cell transplant (ASCT), all 7 BMT pts died a median of 1 (range 1–14) month post-BMT while 4/8 NMT pts remained alive 8, 21, 29, and 33 months post-NMT. By multivariate analysis, BMT (HR 7.74, 95% CI 2.49–24.0, P<.001), HL (HR 6.52, 95% CI 2.04-20-85, P=.002), prior ASCT (HR 3.33, 95% CI 1.20–9.25, P=.021), and increasing age by decade (HR 1.7, 95% CI 1.11–2.62, P=0.14) were associated with a significantly higher mortality while CR/PR at tx was associated with a significantly lower mortality (HR 0.44, 95% CI 0.21–0.93, P=.032). Restricting the multivariate analysis to the 56 NHL pts identified no significant independent prognostic factors. Finally, excluding the 15 pts with prior ASCT showed that BMT, >3 prior chemotherapy regimens, tumor >10 cm at diagnosis, older age, and no remission at tx were all associated with a significantly higher mortality. We conclude that: 1) lymphoma progression and lymphoma- or transplant-related death beyond 2 years are uncommon; 2) BMT after failed ASCT is uniformly fatal while NMT (even after failed ASCT) may lead to long-term survival; 3) GVHD (with its presumed graft vs. lymhoma effect) is important for long-term, progression-free survival; 4) compared to BMT, NMT is associated with a better OS (although pt selection may account for some of the observed difference), and 5) both NMT and BMT are appropriate options for selected NHL pts. Whether NMT or BMT offers any benefit compared to ASCT for HL pts is unclear. Figure Figure

scholarly journals Allogeneic Stem Cell Transplantation in Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 55
Author(s):  
Christine Greil ◽  
Monika Engelhardt ◽  
Jürgen Finke ◽  
Ralph Wäsch
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Risk Groups ◽  
High Dose ◽  
Term Survival ◽  
Hematopoietic Stem

The development of new inhibitory and immunological agents and combination therapies significantly improved response rates and survival of patients diagnosed with multiple myeloma (MM) in the last decade, but the disease is still considered to be incurable by current standards and the prognosis is dismal especially in high-risk groups and in relapsed and/or refractory patients. Allogeneic hematopoietic stem cell transplantation (allo-SCT) may enable long-term survival and even cure for individual patients via an immune-mediated graft-versus-myeloma (GvM) effect, but remains controversial due to relevant transplant-related risks, particularly immunosuppression and graft-versus-host disease, and a substantial non-relapse mortality. The decreased risk of disease progression may outweigh this treatment-related toxicity for young, fit patients in high-risk constellations with otherwise often poor long-term prognosis. Here, allo-SCT should be considered within clinical trials in first-line as part of a tandem approach to separate myeloablation achieved by high-dose chemotherapy with autologous SCT, and following allo-SCT with a reduced-intensity conditioning to minimize treatment-related organ toxicities but allow GvM effect. Our review aims to better define the role of allo-SCT in myeloma treatment particularly in the context of new immunomodulatory approaches.

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.

scholarly journals Long term follow-up report of cardiac toxicity in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantation

2013 ◽  
Vol 47 (2) ◽  
pp. 161-165 ◽  
Author(s):  
Mirta Kozelj ◽  
Samo Zver ◽  
Vesna Zadnik
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Side Effects ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
High Dose ◽  
Hematopoietic Stem

Background. Tandem autologous hematopoietic stem cell transplantation (ta-HSCT) is a standard treatment for multiple myeloma (MM). Patients receive a high-dose cyclophosphamide (CY), followed by two myeloablative cycles of melphalan (MEL). There are scarce data about long term cardiotoxicity. Patients and methods. We studied 12 patients (62.25 ± 8.55 years) six years after the completion of MM treatment with ta-HCST. Late cardiotoxic effects were evaluated clinically and echocardiographically. Results. None of the patients developed clinical signs of heart failure, all were in sinus rhythm and NT-pro BNP concentration was elevated (778 ± 902.76 pg/mL). The left ventricular (LV) size remained normal. The LV ejection fraction did not decrease (73.75 ± 5.67%, 69.27 ± 6.13%, p = NS). The LV diastolic function parameters (E, A, ratio E/A and A/a) did not change significantly. In tissue Doppler parameters we observed a nonsignificant decrease in Em (10.26 ± 2.63 cm/s, 7.57 ± 1.43 cm/s) and Sm velocities (8.7 ± 0.87 cm/s, 7.14 ± 1.17 cm/s, p = NS). The E/Em values were in an abnormal range (8.66 ± 1.05, 10.55 ± 2.03). Conclusions. The treatment of MM with ta-HSCT, during which patients receive a high dose CY followed by two myeloablative cycles of MEL, causes mild, chronic, partially reversible and clinically silent cardiotoxic side-effects. However, ta-HSCT in patients with MM is a safe regarding cardiotoxic side effects, but, because of increasing life expectancy needs long term attention.

scholarly journals Prediction of Response and Survival Following Treatment with Azacitidine for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes after Allogeneic Hematopoietic Stem Cell Transplantation

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2255 ◽  
Author(s):  
Christina Rautenberg ◽  
Anika Bergmann ◽  
Ulrich Germing ◽  
Caroline Fischermanns ◽  
Sabrina Pechtel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Term Outcome ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Outcome

To provide long-term outcome data and predictors for response and survival, we retrospectively analyzed all 151 patients with relapse of myeloid neoplasms after allogeneic hematopoietic stem cell transplantation (allo-HSCT) who were uniformly treated with first-line azacitidine (Aza) salvage therapy at our center. Patients were treated for molecular (39%) or hematologic relapse (61%), with a median of 5 cycles of Aza and at least one donor lymphocyte infusion in 70% of patients. Overall response was 46%, with 41% achieving complete (CR) and 5% achieving partial remission. CR was achieved after a median of 4 cycles and lasted for a median of 11 months (range 0.9 to 120 months). With a median follow-up of 22 months (range: 1 to 122 months), the 2-year survival rate was 38% ± 9%, including 17 patients with ongoing remission for >5 years. Based on results from multivariate analyses, molecular relapse and time to relapse were integrated into a score, clearly dividing patients into 3 subgroups with CR rates of 71%, 39%, and 29%; and 2-year survival rates of 64%, 38%, and 27%, respectively. In the subgroup of MDS and secondary AML, receiving upfront transplantation was associated with superior response and survival, and therefore pretransplant strategy was integrated together with relapse type into a MDS–sAML-specific score. Overall, Aza enables meaningful responses and long-term survival, which is a predictable with a simple-to-use scoring system.

Negative Impact of Pre-Transplant Anemia on Long-Term Outcome after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1844-1844
Author(s):  
Chris Lazongas ◽  
Cindy J. Wong ◽  
David M. Sutton ◽  
Jeffrey H. Lipton ◽  
Anargyros Xenocostas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Causes Of Death ◽  
Term Survival ◽  
Hematopoietic Stem

Abstract Background: Anemia is commonly present in patients with malignancies and is associated with reduced survival times. Recently, we described that low (<110 g/L) pre-transplant hemoglobin levels (PT-Hb) are associated with decreased early survival after allogeneic hematopoietic stem cell transplantation (alloHSCT)(Xenocostas et al. Transfusion2003;43:373–382). We are now presenting data on long-term survival and causes of death in BMT recipients with and without anemia prior to alloHSCT. Study Design and Methods: A retrospective analysis of 511 patients consecutively transplanted between January 1995 and March 2000 was performed to evaluate survival, cause of death, and PT-Hb. The end date for follow-up was June 2002. The median follow-up time was 993 days. Causes of death were categorized either as relapse, treatment-related mortality (TRM), or other. PT-Hb levels were determined within 2 weeks prior to transplantation, after commencing conditioning chemotherapy. Comparisons between groups were done using chi-squared tests. Results: The 180-day survival of patients with low PT-Hb levels (<110 g/L) was significantly worse than that of patients with PT-Hb levels ≥110 g/L (57.1% versus 83.1%, p<0.0001). The survival difference remained significant at 5 years (36.2% versus 59.4%, p<0.0001). The difference in 180-day survival was contributed to by an increase in TRM (36.1% versus 14.9%, p<0.0001) as well as a higher relapse rate (4.4% versus 0.3%, p=0.019 by Fisher’s exact test). For patients surviving more than 180 days, there was no difference in TRM (16.7% versus 16.7%, p=0.987) or relapse rate (12.0% versus 7.3%, p=0.150). No difference in the rate of other causes of death was found between the groups at either the 180-day or 5-year time points. Conclusions: Pre-transplant anemia is an independent risk factor for increased mortality following alloHSCT. Relapse and treatment-related deaths are both more likely to occur early in the post-transplant course of patients experiencing pre-transplant anemia. Differences in long-term survival are predominantly related to treatment-related deaths rather than relapse.

Case Report: Haploidentical Stem Cell Transplantation In a 78 Year-Old Patient

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5468-5468
Author(s):  
Thiago Xavier Carneiro ◽  
André Domingues Pereira ◽  
Theodora Karnakis ◽  
Celso Arrais Rodrigues
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Post Transplant

Abstract An older chronologic age has been a consistent predictor of poor outcomes in hematopoietic stem cell transplantation (HSCT), mainly due to non-relapse mortality (NRM). Therefore, non-curative treatment strategies are commonly adopted for these patients. However, mortality and treatment toxicity has decreased as a result of improved supportive measures, such as reduced intensity conditioning regimens and optimized infection management. T-cell replete haploidentical HSCT emerged as a feasible alternative for leukemia patients without substantial differences in outcomes when compared to fully matched related donor. We report an old adult woman treated with haploidentical HSCT. A 78 year-old female patient presented with anemia, leukocytosis, thrombocytopenia and blasts in the peripheral blood. Diagnosis of acute myelogenous leukemia was established. Conventional cytogenetic demonstrated chromosome eight trisomy, and FISH was negative for other common MDS/AML cytogenetic abnormalities. FLT3-ITD and NPM1 mutations were negative. Her medical history was negative except for heavy smoking. Considering the patients advanced age, the first attending physician chose not to administer intensive treatment and started on decitabine 20 mg/m2 for 5 days. She was refractory to the first-line treatment with persistent cytopenias and blasts in the peripheral blood four weeks after treatment was started. Comprehensive geriatric assessment was performed. She was considered independent for Basic Activities of Daily Living (ADL score 6) and Instrumental Activities of Daily Living (IADL score 27), without cognitive impairment in mini-mental state examination (MMSE score 30), at risk of malnutrition in mini nutritional assessment (MNA 9). As she was considered fit, we decided to perform high-dose chemotherapy with idarubicin and cytarabine, but, once more, the disease was refractory. A rescue regimen was attempted with high-dose cytarabine and mitoxantrone, again, with no response. After discussing pros and cons with the patient and the family, we decided to start Another regimen consisting of topotecan and high dose cytarabine immediately followed by allogeneic hematopoietic stem cell transplantation (HSCT). At day 14, she had 3% blasts in the BM aspirate a T-cell replete haploidentical HSCT using her 52 year-old son as donor and mobilized peripheral blood as stem cell source was performed. Conditioning regimen consisted of fludarabine, cyclophosphamide, TBI 2Gy and post-transplant cyclophosphamide. Graft versus host disease (GVHD) prophylaxis consisted of mycophenolate mofetil and cyclosporine. She had neutrophil engraftment with complete donor chimerism at day+15 and platelet engraftment at day+17. At day+48, she had mild (stage II) skin acute GVHD resolved with topical steroids. Cyclosporine was withdrawn at day+ 93. Due to high relapse risk, the patient was started on monthly post-transplant azacitidine 36 mg/m2. At day+100 the patient remained in complete remission, complete donor chimerism in peripheral blood and bone marrow. Functionality was preserved (ADL score 6 and IADL score 24), presented discrete cognitive impairment (MMSE 28) and malnoutrition (MNA 5). She is now at day+182, doing well and performing again all usual daily activities. To the best of our knowledge, this is the oldest patient treated with haploidentical HSCT. Post transplant cyclophosphamide as T cell depletion strategy in haploidentical HSCT is well tolerated and widely available, being therefore an excellent alternative for patients without conventional donors who require immediate transplant. Older adults with hematologic malignancies are a heterogeneous group and decisions based on chronological age alone are clearly inappropriate. Recently, geriatric assessment proved to be an important prognostic tool in acute leukemia and may be useful in HSCT. In experienced centers, haploidentical HSCT in older adults may be a safe procedure and more accurate pre-transplantation risk stratification tools should be developed. Figure 1 Timeline of main events during hematopoietic stem cell transplant. Figure 1. Timeline of main events during hematopoietic stem cell transplant. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Long-Term Survival After Hematopoietic Stem Cell Transplantation for Complete STAT1 Deficiency

2017 ◽  
Vol 37 (7) ◽  
pp. 701-706 ◽  
Author(s):  
Samuele Naviglio ◽  
Elena Soncini ◽  
Donatella Vairo ◽  
Arnalda Lanfranchi ◽  
Raffaele Badolato ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival

scholarly journals Allogeneic stem cell transplantation mitigates the adverse prognostic impact of high diagnostic BAALC and MN1 expression in AML

2020 ◽  
Vol 99 (10) ◽  
pp. 2417-2427
Author(s):  
Madlen Jentzsch ◽  
Marius Bill ◽  
Juliane Grimm ◽  
Dominic Brauer ◽  
Donata Backhaus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Prognostic Impact ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Copy Numbers ◽  
Droplet Pcr

Abstract For most acute myeloid leukemia (AML) patients, an allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance of sustained remissions and long-term survival. At diagnosis, high expression of the AML-associated genes BAALC (brain and acute leukemia, cytoplasmic) and MN1 (meningioma-1) were repeatedly linked to inferior outcomes in patients consolidated with chemotherapy while data for patients receiving HSCT remain limited. Using clinically applicable digital droplet PCR assays, we analyzed the diagnostic BAALC/ABL1 and MN1/ABL1 copy numbers in 302 AML patients. High BAALC/ABL1 and MN1/ABL1 copy numbers associated with common adverse prognostic factors at diagnosis. However, while high diagnostic copy numbers of both genes associated with shorter event free survival (EFS) and overall survival (OS) in patients receiving chemotherapy, there was no prognostic impact in patients undergoing HSCT. Our data suggests that the adverse prognostic impact of high BAALC and MN1 expression are mitigated by allogeneic HSCT. But preHSCT BAALC/ABL1 and MN1/ABL1 assessed in remission prior to HSCT remained prognosticators for EFS and OS independent of the diagnostic expression status. Whether allogeneic HSCT may improve survival for AML patients with high diagnostic BAALC or MN1 expression should be investigated prospectively and may improve informed decisions towards individualized consolidation options in AML.

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