Clinical Status Longer than One Year Post-Transplantation in 4 Recipients of Non-T-Cell-Depleted HLA-Haploidentical Transplantation Based on Feto-Maternal Microchimerism.

Abstract The long-term presence of fetal hematopoietic cells in the maternal blood after childbirth indicates maternal tolerance to fetal inherited paternal antigens (IPA), and also that of maternal hematopoietic cells in the offspring’s blood after birth indicates mutual tolerance to non-inherited maternal antigens (NIMA) among sibling. Based on such recent feto-maternal microchimerism / tolerance theory, more than 40 cases have received non-T-cell-depleted (non-TCD) HLA-haploidentical stem cell transplantation (SCT) for various hematological malignancies in Japan. Their early post-SCT clinical courses have been reported; however, long-term outcome and quality of life of such SCT recipients are largely unknown. In our hospitals, we used non-TCD cells from haploidentical family donors for transplantation in 5 children with hematologic malignancies. Among those children, four have been alive for more than one year. Three of the 4 recipients still require prophylactic immunosuppressants for chronic GVHD. Only one case developed chronic GVHD (skin limited). Various late complications are noted in 3. Three children showed complete school attendance. Two of the three are also allowed to participate in physical exercises. These results suggest that quality of life in long-term survivors in childhood from non-TCD HLA-haploidentical SCT based on feto-maternal microchimerism seems acceptable although the numbers are still small and the follow-up period is short. Patients characteristics Case Age Diagnosis Status Donor HLA mismatch acute GVHD Survival after SCT (days) 1 6 ALL CR1 (advanced remission) NIMA-mismatched sibling 2 2 CR, 802+ 2 11 ALL Rejection after UCBT (CR2) Mother 2 1 CR, 775+ 3 16 MLL Refractory relapse after UCBT Mother 2 1 CR, 519+ 4 14 CML Blastic phase Mother 2 1 CR, 473+ 5 6 ALL Rejection after UCBT (Rel 1) Mother 3 2 Dead, 93 Present status of long-term survivors Case chronic GVHD Karnofsky score Late complications School attendance Physical exercise Medication 1 - 100 - complete permitted - 2 - 100 hypothyroidism complete permitted FK506 3 + (skin) 70 diabetes, esophageal stricture no prohibited PSL+MTX, insulin 4 - 100 arrhythmia complete prohibited FK506

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Reduced-Intensity Conditioning Is Associated with Shorter Duration of Chronic GVHD Than Myeloablative Conditioning and Provides Very Good Quality of Life for Long-Term Survivors after Allogeneic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v110.11.1668.1668 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1668-1668

Author(s):

Avichai Shimoni ◽

Izhar Hardan ◽

Noga Shem-Tov ◽

Avital Rand ◽

Elena Ribakovsky ◽

...

Keyword(s):

Quality Of Life ◽

Acute Leukemia ◽

Chronic Gvhd ◽

Cumulative Probability ◽

Reduced Intensity Conditioning ◽

Lymphoid Malignancies ◽

Long Term Survivors

Abstract Reduced-intensity conditioning (RIC) has been increasingly used over the last decade as a curative approach for patients (pts) not eligible for myeloablative (MA) conditioning. It is now established that RIC can allow consistent engraftment and reduce toxicity of allogeneic stem-cell transplantation (SCT). However, the long-term effects, and in particular the duration of immunosuppressive therapy (IST) needed and quality of life of long-term survivors are less defined. To explore these issues we analyzed the results of 48 pts given SCT with RIC from 1/2000 to 8/2002, such that survivors have at least 5 year follow-up, and compared them to results of 41 SCT with MA conditioning given during the same period. The RIC group included older pts than the MA group, median age 49 (range, 20–65) and 37 (range, 20–65), respectively (p=0.01). The MA group included more pts with acute leukemia/MDS (68% vs 33%, p=0.001) while pts with myeloma were only given RIC (31% of the RIC group, p< 0.001). 48% of pts in the RIC group had a prior autologous SCT compared with none in the MA group (p< 0.001). There was no difference in donor type, 26% of all pts were given SCT from unrelated donors. After a median follow-up of 6.1 years (range, 5.1–7.6) 40 pts are alive, 20 after RIC and 20 after MA conditioning with estimated survival of 42% (95ci, 28–56) and 47% (95ci, 31–63), respectively (p=NS). Long-term survival with RIC was achieved across all diagnoses including 6 of 16 pts with acute leukemia/MDS, 6 of 6 pts with CML, 3 of 11 pts with lymphoid malignancies and 5 of 15 pts with myeloma. The corresponding rates for acute leukemia/MDS, CML and lymphoid malignancies in the MA group were 13 of 28, 3 of 4 and 4 of 9, respectively. Chronic GVHD occurred in 22 pts after RIC and in 26 pts after MA conditioning with a cumulative incidence of 48% (35–65) and 66% (53–83), respectively (p=0.07). 12 of 22 pts with chronic GVHD after RIC were eventually able to stop IST, 9 died on IST (relapse-5, non-relapse mortality (NRM)-4) and only 1 of 20 long-term survivors was still on IST at last follow-up. The median duration of IST was 17 months and the cumulative probability of stopping IST after 5 years (with relapse been competing risk) was 79%. In the MA group 10 of 26 pts with chronic GVHD were able to stop IST, 8 died on IST (relapse-6, NRM-2) and 8 of 20 long-term survivors were still on IST at last follow-up. The median duration of IST was 41 months (p=0.05) and the cumulative probability of stopping IST after 5 years was 48% (p=0.001). Two women gave birth in the RIC group while 2 men in the MA group fathered children spontaneously. There was one secondary malignancy in the MA group and none in the RIC group. Two pts in the MA group sustained myocardial infarction (one fatal) compared to none of the RIC group. One pt in the RIC group had reversible nephrotic syndrome. In summary long term(>5y) survival is similar for both RIC and MA SCT, however IST is significantly shorter after RIC and quality of life seems better. Overall, all 20 pts surviving more than 5 years after RIC SCT sustained excellent quality of life and only one still required IST. The more rapid achievement of transplantation tolerance with RIC may relate to better preservation of thymic function, but this requires further investigation. These observations require further confirmation in larger registry studies.

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