Acute myeloid leukemia of donor origin after allogeneic bone marrow transplantation for precursor T-cell acute lymphoblastic leukemia: Case report and review of the literature

In 1997, a 55-year-old woman with Philadelphia chromosome positive CML in the first chronic phase received allogeneic peripheral blood SCT from her HLA-identical sister following a preparative regimen containing CY (total dose of 120 mg/kg) and fractionated TBI (2.4 Gy Â 6). Standard GVHD prophylaxis was provided by methotrexate and CYA. Earlier transplantation donor examination showed a normal full blood count with a normal leukocyte count and normal lymphocyte percentage. From day þ 100 after transplant onwards, real-time PCR showed a bcr-abl/ abl ratio consistent with complete molecular remission of CML and complete donor chimerism was found by molecular studies. Grades 1-2 acute and subsequently limited chronic GVHD of the skin and mouth mucosa had developed as transplant complication and responded well to steroid treatment. Until 2005, normal leukocyte counts and normal lymphocyte percentages were repeatedly found on follow-up blood tests.In early 2005, a slightly elevated leukocytosis of 13.6/nl was detected for the first time but was not investigated further. One year later, the patient presented with elevated leukocyte count of 21/nl and a lymphocytosis at 78% while being without clinical symptoms. Haemoglobin level and platelet count were normal at 13.3 g per 100 ml and 247/nl, respectively. No palpable lymph nodes were found on clinical examination, spleen and liver were not enlarged, chest X-ray and abdominal ultrasound yielded unremarkable results. Immunophenotyping was performed on peripheral blood and showed a B lymphocyte clone with the immunophenotype CD19 þ /CD20 þ low/CD5 þ / CD22 þ low/CD23 þ /FMC7À/CD24 þ /CD79bÀ/CD43 þ / ZAP-70À compatible with CLL stratified stage A according to Binet classification. Cytogenetics showed a normal karyotype by banding techniques, whereas interphase FISH revealed a deletion at 13q14 and additional chromosomal material at 12q13, but was negative for 6q21, 8q24, 11q22.3 and 17p13 abnormalities. Immunoglobulin heavy chain gene sequencing of the CLL clone revealed a highly mutated gene status (410% mutation rate, VH 4-34 DH 5-24 JH 4*02). Chimerism studies using short tandem repeats amplification of nine loci showed 100% donor chimerism in both the CD3-positive and in the CD19-positive cell fraction demonstrating donor origin of T-cells and B-cells. Subsequently, blood tests were performed on the 76-year-old stem cell donor. The leukocyte count was slightly elevated but no lymphocytosis was detected. Interestingly, immunophenotyping of donor's peripheral blood showed the presence of a B-cell clone with the(13% of all lymphocytes). Clonal identity with the recipient's CLL clone was documented in the donor's blood samples by quantitative Ig heavy chain allele-specific oligonucleotide PCR using clone-specific forward primers in combination with heavy chain immunoglobulin J segment (JH) family-specific consensus reverse primers and probes as described earlier.

supporting

confidence: 85%

Occurrence of donor-derived CLL 8 years after sibling donor SCT for CML

Perz

Ritgen²,

Moos

et al. 2008

“…We excluded five cases from the report of Cooley 36 because four cases overlapped with cases from the report of Hertenstein 41 and because the abnormal karyotype of the recipient continued to be present in the other case. We also excluded 20 cases from Reichard et al 50 because they overlapped with those in Cooley et al 36 and in Hertenstein et al 41 The numbers of men and women were similar (25/27), and the median age of the patients was 31.0 years (range: 3-66 years). The median duration between BMT and the occurrence of DCL was 36 months (range: 2-312 months).…”

Section: Donor Cell Leukemia After Cbt H Shiozaki Et Almentioning

confidence: 99%

Donor cell-derived leukemia after cord blood transplantation and a review of the literature: differences between cord blood and BM as the transplant source

Shiozaki

Yoshinaga

Kondo

et al. 2013

Donor cell-derived leukemia (DCL) is a rare complication of SCT. Here, we present a case of DCL following cord blood transplantation (CBT) and review the clinical features of previously reported DCL. To our knowledge, this is the first report comparing clinical characteristics of DCL from the standpoint of the transplant source, with umbilical cord blood and BM. AML and myelodysplastic syndrome (MDS) were recognized more frequently in DCL after CBT, whereas the incidence of AML and ALL was similar after BMT. The median duration between the occurrence of DCL following CBT and BMT was 14.5 and 36 months, respectively. DCL occurred in a significantly shorter period after CBT than after BMT. Abnormal karyotypes involving chromosome 7 were observed in 52.4% of CBT recipients and 17.3% of BMT recipients; this was a statistically significant difference. Particularly, the frequency of monosomy 7 was significantly higher in DCL after CBT than after BMT. The types of abnormal karyotypes in DCL following BMT were similar to those characteristically observed in adult de novo AML and MDS. DCL patients generally have a poor prognosis in both groups. SCT is the best treatment for curing DCL. DCL appears to have different clinical features according to the transplant source.

“…1,2 Since donor cell leukemia is such a rare phenomenon, treatment of these patients has not been standardized. In this report, we present a child with pre-B ALL who developed a secondary AML of donor origin with Mixed-lineage leukemia (MLL) gene rearrangement after treatment for a relapse of his ALL after allogeneic BMT.…”

mentioning

confidence: 99%

Therapy-related, donor-derived AML responding to a second allogeneic BMT

Jacobs

Brons

Simons

et al. 2007

Donor cell leukemia is a rare complication of allogeneic BMT, and many hypotheses about the underlying mechanisms have been put forth.1,2 Since donor cell leukemia is such a rare phenomenon, treatment of these patients has not been standardized. In this report, we present a child with pre-B ALL who developed a secondary AML of donor origin with Mixed-lineage leukemia (MLL) gene rearrangement after treatment for a relapse of his ALL after allogeneic BMT. A second allogeneic BMT with marrow from the same donor was performed and the patient is in ongoing complete remission now for 4 years. Our data show that long-lasting remission can be achieved after donor-derived, therapy-related AML by a second transplant with marrow from the same donor.A 1-year-old, Caucasian boy with recurrent infections was diagnosed with ALL FAB L1 in 1988 and he was treated according to the ALL-BFM-86 regimen. In a period of 10 years, he relapsed twice (Figures 1a and b). Flow