Second Allogeneic Stem Cell Transplantation in Myeloid Malignancies

Hartwig, Maite; Ocheni, S; Asenova, Svetlana; Wiedemann, B; Zabelina, Tatjana; Ayuk, Francis; Kabisch, H; Erttmann, R.; Zander, Axel R.; Bacher, Ulrike

doi:10.1159/000253025

Cited by 18 publications

(21 citation statements)

References 55 publications

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“…9 Nevertheless, second SCT carries a high risk of treatment failure, both from relapse and non-relapse mortality. 14 Because patients relapsing after SCT show diversity in the aggressiveness and chemosensitivity of their disease, and vary widely in their performance status, second transplants tend to be offered on an individual basis to selected patients, usually those with better disease control and good performance status. An additional factor determining treatment for relapse is dictated by patient preference for either further intensive treatment or palliative measures, and the availability of donor.…”

Section: Discussionmentioning

confidence: 99%

Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival

McIver

Yin

Hughes

et al. 2013

Bone Marrow Transplant

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Patients with leukemia relapsing after allogeneic hematopoietic stem cell transplantation (SCT) have a dismal prognosis. A second SCT offers a further opportunity for cure, but has a high rate of treatment failure. To determine the utility of this option, we analyzed 59 consecutive patients relapsing after a myeloablative HLA-matched sibling T cell depleted SCT. Twenty five patients (13 relapsing within 6 months and 12 relapsing between 6 – 170 months after the first SCT) received a T-replete second SCT. Thirty-eight patients relapsing early had a shorter survival than the 21 patients relapsing later (median 96 vs 298 days, p = 0.0002). In patients relapsing early, the second SCT did not improve overall survival compared to patients receiving non-SCT treatments (median survival 109 vs 80 days, p = 0.41). In patients relapsing late, despite an early trend in favor of second SCT, overall survival was comparable for patients receiving a second SCT compared with patients not retransplanted (median survival 363.5 vs 162 days, p = 0.49). Disappointingly our results do not demonstrate an important survival benefit for a second T-replete allogeneic SCT to treat relapse following a T cell depleted SCT.

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Section: Discussionmentioning

confidence: 99%

Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival

McIver

Yin

Hughes

et al. 2013

Bone Marrow Transplant

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“…We performed SCT3 using CB in seven patients. There were several single case reports, or reports of several cases within reports of SCT2, of patients who received SCT3 for relapsed leukemia after SCT2 [3,4,19,20]. However, these reports did not describe the conditioning regimens and GVHD prophylaxis or the outcomes of SCT3 in detail, or the observation period was limited.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the change of the donor for SCT3 by CB might induce a graft-versus-leukemia (GVL) effect mediated by the different CB. There have been numerous reports of SCT2 for relapsed leukemia after SCT1 [1][2][3][4][5][6][7][8][9][10][11][12][13]. However, the efficacy of SCT3 for patients with relapsed leukemia after SCT2 is unknown.…”

Section: Introductionmentioning

confidence: 99%

Third allogeneic stem cell transplantation (SCT) using unrelated cord blood for relapsed acute leukemia after second allogeneic SCT

et al. 2015

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We analyzed the results of third allogeneic stem cell transplantation (SCT3) using single-unit unrelated cord blood (CB) in seven adult patients with relapsed acute leukemia after second allogeneic stem cell transplantation (SCT2). The median age at SCT 3 was 44 years (range 20-58 years). The patients had de novo acute myeloid leukemia (AML) (n = 4), secondary AML following myelodysplastic syndrome (n = 2), and acute lymphoblastic leukemia (n = 1). Four patients received myeloablative conditioning, and three received reduced-intensity conditioning. All but one patient had myeloid reconstitution with remission, but five patients relapsed even after SCT3. However, one patient is alive and disease-free 6 years after SCT3, which is the longest remission duration among three allogeneic SCTs she received. Furthermore, actual survival after relapse of SCT 2 was significantly better for patients who received SCT3 compared with institutional control patients who never received SCT3 (P < 0.001). These results suggest that the use of CB may allow the opportunity to perform SCT3 in patients who have experienced relapsed leukemia without donors, and SCT3 with CB may offer the chance of durable remission for selected patients with relapsed acute leukemia.

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“…47 In a second study, 24% of patients remained in remission after a median follow-up of 18 months. 48 Patients for whom HCT2 is considered should have an excellent performance status as the rate of transplant-related mortality approaches 45%. Elderly patients and, those receiving both HCTs within 6 months, are at the greatest risk of transplant-related mortality.…”

Section: Consolidationmentioning

confidence: 99%

The devil is in the T cells: relapsing after haploidentical hematopoietic cell transplantation

Byrne

Savani

2016

Bone Marrow Transplant

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For several decades, allogeneic hematopoietic cell transplantation (HCT) has remained an important tool in the management of patients with high-risk hematological malignancies. Reduced intensity conditioning regimens and advances in supportive care have improved the safety and accessibility of HCT and also increased the need for a deep and diverse stem cell donor pool. This demand has highlighted existing disparities in the unrelated donor registry, particularly for ethnic minorities, who face significant challenges in identifying HLA-matched adult donors. 1 The acceptance of umbilical cord blood and haploidentical grafts as viable 'alternative' donors has increased the options for these patients and now ensures that a donor can be identified for virtually all patients.The utilization of haploidentical grafts represents appealing options owing to their ubiquity, low cost and donor availability for future lymphocyte accession compared with umbilical cord blood units. Haploidentical grafts, however, lack the long-term follow-up of traditional stem cell sources resulting in several areas where the optimal management strategy remains unknown. With a growing number of patients receiving HCTs from haploidentical sources in the United States and abroad, advancing the care of these patients represents an area of tremendous interest and clinical necessity. 2 Two decades ago, Beatty et al. 3 first reported their experience with HLA-disparate allografts. The patients had high rates of graft rejection and acute GVHD (aGVHD) that was nearly double the HLAmatched control group. Over the following decade, animal studies with post-HCT cyclophosphamide demonstrated encouraging results and gave way to two early-phase studies. [4][5][6] Mechanistically, post-transplant cyclophosphamide reduces the robust, alloantigendirected, naive T-lymphocyte population after stem cell infusion. 7 With posttransplant cyclophosphamide, the rates of aGVHD are substantially reduced. 8,9 Subsequent work in 2008 confirmed minimal aGVHD; however, more than half of patients relapsed within 1 year and 2-year overall survival was a staggering 36%. 10 Parallel, multicenter trials were published 3 years later comparing double umbilical cord blood units with haploidentical grafts. After a median follow-up of 357 days, 45% of haploidentical patients relapsed and 62% were still alive 1 year after HCT. 11 The use of post-transplant cyclophosphamide was championed as a measure that advanced the safety of haploidentical HCT through diminished rates of aGHVD. GVHD, and the coveted GVL effects, are dogmatically linked and drive the long-term remissions seen in survivors. 12,13 In spite of these low rates of aGVHD, improvements in the post-HCT management of these patients translated into improved clinical outcomes. 10,[14][15][16][17][18][19][20][21][22][23][24] Relapsed disease is a principal threat to these patients' longterm survival and affects 30-50% of our patients. [25][26][27] Relapse is driven by an aggressive disease biology that can be difficult and in m...

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Second Allogeneic Stem Cell Transplantation in Myeloid Malignancies

Cited by 18 publications

References 55 publications

Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival

Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival

Third allogeneic stem cell transplantation (SCT) using unrelated cord blood for relapsed acute leukemia after second allogeneic SCT

The devil is in the T cells: relapsing after haploidentical hematopoietic cell transplantation

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