Non-myeloablative Peripheral Blood Stem Cell Research Articles

Post-Transplant Maintenance in AML and MDS Patients Undergoing Non-Myeloablative Peripheral Blood Stem Cell Transplant with Post-Transplant Cyclophosphamide

Post-Transplant Maintenance in AML and MDS Patients Undergoing Non-Myeloablative Peripheral Blood Stem Cell Transplant with Post-Transplant Cyclophosphamide

Post-Transplant Maintenance in AML and MDS Patients Undergoing Non-Myeloablative Peripheral Blood Stem Cell Transplant with Post-Transplant Cyclophosphamide

Disease relapse remains a major cause of mortality for patients with AML and MDS undergoing allogeneic hematopoietic stem cell transplant (HSCT). Several trials have evaluated the use of hypomethylating agents (HMA) like azacitadine or decitabine as post-transplant maintenance with its use not currently recommended. Here we review our experience with AML and MDS patients undergoing non-myeloablative (NMA) peripheral blood stem cell transplant using post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis and in whom post-transplant maintenance was used. We retrospectively reviewed AML and MDS patients who had a NMA HSCT from January 2015 until December 2022. All patients received fludarabine, cyclophosphamide and TBI200 or TBI300 as conditioning regimen with tacrolimus, mycophenolate mofetil and PTCy as GVHD prophylaxis (Table 1). Sixty patients received TBI200 and 28 patients received TBI300. Median age at transplant was 65.5 years in the TBI200 group vs 69 years in the TBI300 group. Haploidentical donors were used in 59 (98%) of patients in the TBI200 group and 18 (64%) of patients in the TBI300 group. Minimal residual disease (MRD) was present 35 (58%) of patients receiving TBI200 and 12 (43%) of patients receiving TBI300. Post-transplant therapy was given in 46 (77%) of patients in the TBI200 group and 23 (82%) in the TBI300 group. The majority of patients in both groups received azacitadine. The median cycles of HMAs was 4 (range 1-12). We found no difference in OS, PFS, relapse, or NRM comparing Flu/Cy/TBI200 and Flu/Cy/TBI300 (not shown). We evaluated the use of post-transplant maintenance on survival endpoints and found no difference in endpoints. In addition, post-transplant maintenance had no effect on OS, PFS, relapse, NRM or grade II-IV aGVHD regardless of MRD status at time of transplant. While, this is a small retrospective series, it warrants further investigation into the use of post-transplant maintenance in the setting of NMA HSCT using PTCy. While the use of HMA's did not increase NRM, their efficacy and perhaps combination with other drugs needs to be more closely studied in NMA PTCy transplants to decrease relapse.

Long--Term Free Survival of Two Class III β-Thalassemic Patients after Non-Myeloablative Stem Cell Transplantation

At present, hematopoietic stem cell transplantation is the only curative treatment for β thalassemia patients. Conventional myeloablative stem cell transplantation is associated with significant morbidity and mortality, and non-myeloablative stem cell transplantation is associated with high graft failure rate. Some modification in this treatment approach can result in successful transplantation in thalassemia patients. Two successful Fludarabine-based non-myeloablative stem cell transplantation in two Class III β thalassemia patients are reported here. The first patient was a 14-year old girl that developed rapid engraftment and full chimerism after rapid tapering of cyclosporine as graft-versus-host disease (GVHD) prophylaxis drug according to our protocol. Another patient was a 24-year old female patient that developed cyclosporine toxicity, and early tapering of cyclosporine helped for rapid engraftment and successful transplantation. After these two successful experiments in non-myeloablative peripheral blood stem cell transplantation for our class III β thalassemia patients, we concluded that Fludarabine-based non-myeloablative stem cell transplantation with adequate number of stem cells at the time of transplantation and rapid tapering of GVHD prophylaxis drugs after transplantation can potentially help for rapid engraftment and successful stem cell transplantation in high risk β-thalassemia patients.

Characterization of Immune Cells Producing Regulatory Cytokines That Mediate Engraftment in Sickle Cell Disease Patients after Haploidentical Peripheral Blood Stem Cell Transplantation

Sickle cell disease (SCD) is an inherited blood disorder in which red blood cells are sickle-shaped as a result of an amino acid alteration from glutamate to valine at the sixth position of the β-globin chain. Hematopoietic stem cell transplant (HSCT) is a curative option for SCD, with both HLA-matched and haploidentical transplant being viable approaches. Stable mixed chimerism and tolerance induction are sufficient to reverse the sickle phenotype. Graft rejection and graft versus host disease may occur following nonmyeloablative haploidentical peripheral blood stem cell transplantation (PBSCT). Various regulatory cytokines have been identified as biomarkers of engraftment in graft transplantation. Previously, we observed that TGF-β, interleukin (IL)-7, and IL-10 cytokines were elevated in engrafted SCD patients as compared to those who rejected their grafts following haploidentical PBSCT. Now, we aim to identify the immune cell populations responsible for producing the above cytokines in both engrafted and rejected patients. The plasma samples of 21 SCD patients who underwent nonmyeloablative haploidentical PBSCT at the National Institutes of Health between March 2010 and September 2015 were evaluated previously by multiplexed magnetic bead enzyme linked immune sorbent assay. Here, we analyzed various immune cells which produce the above regulatory cytokines through multi-color flow cytometry in 8 out of the 21 patients (four engrafted and four rejected). We evaluated the cytokine producing capabilities via intracellular cytokine detection among T regulatory (Treg, CD3+CD4+CD25+Foxp3+) cells, Type 1 regulatory (Tr1, CD3+CD4+Foxp3-CD45RA-CD49+LAG3+) T cells, T helper 1 (Th1, CD3+CD4+Foxp3-CD45RO+CXCR3+) cells, T helper 17 (Th17, CD3+CD4+Foxp3-CD45RO+CCR6+) cells, natural killer (NK, CD3-CD56+NKG2D+) cells, B regulatory (Breg, CD3-CD56-CD19+CD24hiCD38hi)cells, polymorphonuclear-myeloid derived suppressor cells (PMN-MDSCs, CD45+CD14-CD15+CD11b+), monocytic-MDSCs (CD45+CD14+CD15-HLADRlow), early-MDSCs (CD45+Lin-HLADR-CD11b+CD33+), myeloid dendritic cells (mDCs, CD45+CD3-CD56-HLADR+CD11c+CD123-), and plasmacytoid dendritic cells (pDCs, CD45+CD3-CD56-HLADR+CD11c-CD123+). Cytokine producing cell frequencies were measured at five timepoints: baseline (day 0) and days 30, 60, 100, and 180 post-transplant (PT). Percentages of intracellular cytokine and cell population frequencies were assessed through flow cytometry analysis and statistical significance was determined by Student's t-test. We noted IL-10-producing Tregs were significantly elevated in engrafted patients at PT day 100 (p< 0.01, see Figure 1). Further, IL-10-producing Th1 cells were significantly higher in engrafted patients on PT day 30 (p< 0.01) and day 100 (p< 0.01). However, rejected patients had significantly higher amounts of IL-10-producing PMN-MDSCs (p< 0.01), and myeloid DCs (p< 0.01, see Figure 2), but their levels were lower than IL10-producing Tregs and Th1 cells of engrafted patients. There were no significantly different alterations of IL-10-producing cell frequencies among other cell populations (Tr1, Th17, NK, Breg, early-MDSCs, monocytic-MDSCs, and pDCs). In addition, there were no significant variations in TGF-β- and IL-7-producing cell frequencies in any of the immune cell populations tested. Overall, the engrafted patients showed higher IL-10-producing Tregs and Th1 cells at PT day 30 and/or day 100, which suggest that the immunosuppressive cytokine IL-10 may play an important role in engraftment. Further analyses with a larger sample size are indicated to evaluate whether IL-10 producing immune regulatory cells may serve as a biomarker to predict transplant outcome. Taken together, continuous regulatory cytokine analysis at serial time points pre- and post-transplant may aid in establishing mechanisms of successful engraftment and tolerance induction. Disclosures No relevant conflicts of interest to declare.

Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell–depleted stem cell transplantation

AbstractNatural killer (NK) cells can enhance engraftment and mediate graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT), but the potency of graft-versus-leukemia mediated by naturally reconstituting NK cells following HSCT is limited. Preclinical studies demonstrate that activation of NK cells using interleukin-15 (IL-15) plus 4-1BBL upregulates activating receptor expression and augments killing capacity. In an effort to amplify the beneficial effects of NK cells post-HSCT, we conducted a first-in-human trial of adoptive transfer of donor-derived IL-15/4-1BBL–activated NK cells (aNK-DLI) following HLA-matched, T-cell–depleted (1-2 × 104 T cells/kg) nonmyeloablative peripheral blood stem cell transplantation in children and young adults with ultra-high-risk solid tumors. aNK-DLI were CD3+-depleted, CD56+-selected lymphocytes, cultured for 9 to 11 days with recombinant human IL-15 plus 4-1BBL+IL-15Rα+ artificial antigen-presenting cells. aNK-DLI demonstrated potent killing capacity and displayed high levels of activating receptor expression. Five of 9 transplant recipients experienced acute graft-versus-host disease (GVHD) following aNK-DLI, with grade 4 GVHD observed in 3 subjects. GVHD was more common in matched unrelated donor vs matched sibling donor recipients and was associated with higher donor CD3 chimerism. Given that the T-cell dose was below the threshold required for GVHD in this setting, we conclude that aNK-DLI contributed to the acute GVHD observed, likely by augmenting underlying T-cell alloreactivity. This trial was registered at www.clinicaltrials.gov as #NCT01287104.

Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation

While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4–1147) days, the median PFS was 100 days (95% confidence interval (CI), 66–128 days), and median OS was 209 days (95% CI, 128–236 days). Patients with chronic GVHD had better survival—median OS 426 days (95% CI, 194–NE days) vs 143 days (95% CI, 114–226 days) (P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC.

Nonmyeloablative Peripheral Blood Stem Cell Transplantation for Chronic Myeloid Leukemia in Chronic and Advanced Phases.

Objective: To study the effect of nonmyeloablative peripheral blood stem cell transplantation(PBSCT) for chronic myelogenous leukemia(CML) in chronic phase(CML-CP) and advanced phase(CML-AP).Methods: Twenty-four CML patients, 16 in CML-CP and 4 in CML-AP underwent nonmyeloablative peripheral blood stem cell transplantation(NST). The conditioning regimen included fludarabine 30mg.m−2.d−1, intravenously(i.v.)×6d, busulphan 4mg.m−2.d−1×2d and CTX 350mg.m−2.d−1×2d combined with or without Ara-C. The donors were HLA-identical (n=20) and 5/6 antigen-matched (n=4).Results: All the patients were successfully engrafted. The mean time needed for increase of the number of neutrophils to more than 0.5×109/L and platelet more than 20×109/L were 13 days and 11.5 days respectively. Among 12 patients, 9 showed complete donor chimerism(CDC) and 3 showed mixed chimerism(MC) at +day 30. At +day 180, 18 patients still alive showed CDC and remained alive after a median follow-up of 24 months (4∼48months). 3 cases died of severe acute GVHD(aGVHD), 1 case of chronic GVHD(cGVHD), 2 cases of interstitial pneumonia(IP) and 1 case of relapse.Conclusion: Nonmyeloablative PBSCT is an effective method for CML patients in chronic phase and advanced phase.Characteristics of 24 CML patients and their donorsPatientAgeGenderDiagnosisDonorHLA140maleCML-APbrotherHLA-identical232maleCML-APbrotherHLA-identical340maleCML-CPbrotherHLA-identical440maleCML-CPbrotherHLA-identical542maleCML-APbrotherHLA-identical624maleCML-APsisterHLA-identical755maleCML-CPsisterHLA-identical832maleCML-CPbrotherHLA-identical936maleCML-CPbrotherHLA-identical1046femaleCML-APsisterHLA-identical1152femaleCML-CPbrotherHLA-identical1260maleCML-CPsisterHLA-identical1345femaleCML-CPbrotherHLA-identical1448maleCML-CPbrotherHLA-identical1533maleCML-CPURD*HLA-identical1635femaleCML-CPURDHLA-identical1740maleCML-CPbrotherHLA-identical1834femaleCML-APsisterHLA-identical twin1954femaleCML-CPbrotherHLA-identical2033maleCML-APURDSubtype mismatched2132maleCML-CPURDSubtype mismatched2242maleCML-CPURDmismatched2350femaleCML-CPURDHLA-identical2446maleCML-CPbrotherHLA-identical*: unrelated donor

Non-myeloablative peripheral blood stem cell transplant in a patient with platelet (HPA) mismatch and pre-existing anti-donor platelet alloantibodies

17541 Background: Platelets display a series of polymorphic epitopes which are known as the human platelet alloantigen (HPA) system. Alloantibodies directed against these HPA epitopes cause platelet destruction resulting in thrombocytopenia and refractoriness to platelet transfusions. We describe the rare and unique clinical course of a 61 year old patient with relapsed Non-Hodgkin’s lymphoma (NHL) who received an HLA matched, sibling, non-myeloablative, peripheral blood stem cell transplant (PBSCT) who had alloantibodies directed against a mismatched donor HPA antigen prior to transplant. Methods: The patient received a conditioning regimen of fludarabine (25 mg/m2 QD x4) and cyclophosphamide (1 g/m2 QD x2) followed by stem cell infusion. Graft versus host disease prophylaxis consisted of cyclosporine (1.5 mg/kg BID) and methotrexate (10 mg/m2 QD x 3) per routine protocol. Additionally, to protect donor platelets against the recipient’s alloantibody, the patient received 500 mg/kg gamma globulin (IVIG) on day -2 and +5. Results: The anticipated period of pancytopenia developed, with neutrophil and platelet engraftment occurring on day 19 and 29, respectively. The patient required only two platelet transfusions and did not experience bleeding. The patient remains in remission four years post transplant. Her platelet count is normal off immunosuppression. Conclusions: We have demonstrated that non-myeloablative transplant is possible in an HPA mismatched graft with detectable recipient anti-donor HPA alloantibodies using IVIG prophalaxis, in addition to routine immunosuppression. This has not been previously reported. We additionally provide a timeline showing time to platelet recovery and anti-platelet antibody kinetics that will be helpful in directing the care of future patients. No significant financial relationships to disclose.

Quantitative Assessment of Hematopoietic Chimerism after Allogeneic Nonmyeloablative Stem Cell Transplantation.

Objective:To establish a method for quantitative analysis of hematopoietic chimerism by polymerase chain reaction (PCR) based on short tandem repeat (STR) locies.To investigate the correlation between the kinetics of chimerism and hematologic engraftment, graft rejection, disease relapse and graft versus host disease (GVHD) after allogeneic nonmyeloablative peripheral blood stem cell transplantation.To guide implementation of therapy at an early stage and to improve patients life quality.Method:Cell dilution experiments were performed by mixing mononuclear cells (MNCs) obtained from peripheral blood samples of unrelated individuals to test the sensitivity, accuracy and linearity of the assay. Quantitative assessment of hematopoietic chimerism was performed by short tandem repeat-polymerase chain reaction(STR-PCR), polyacrylamide gels, silver staining and analyzed by Image Analysis System.28 patients received nonmyeloablative stem cell transplantation were evaluated. The conditioning regimen included fludarabine 30mg/(m2·d)×6d, busulphan 4mg/(kg·d)×2d, CTX 600mg·d−1×2d, ±Ara-C.Peripheral blood were collected before and after transplantation in different period and the chimerism were analysed by this method.Results:Sensitivity varied from 1.25% to 5% depending on the STR locies being tested. vWA and D16S539 appeared better sensitivity from 1.25% to 2.5% than other locies. The quantitative results showed a linear correlation between the percent chimerism calculated and the DC proportion mixed(R2 =0.97~0.98, P<0.001). As an average of all informative markers, concordance between the calculated and mixed DC percent showed minimal deviation from 1(R2=0.996).On day 30, one patient failed to engraft, 22 cases formed complete chimerism (CC) and 5 cases were of mixed chimerism (MC).The time of molecular engraftment preceded the recovery time of neutropils and platelets. One patient with MC rejected grafts. The incidence of aGVHD in group CC was significantly higher than that in group MC(P<0.05). There was no significant difference in the incidence of cGVHD and disease relapse between group CC and group MC(P>0.05). One patient relapsed in CC status lacking a transitional MC interveral. Patients received an early implementation of therapy transferred from MC to CC or got a longer disease-free time.Conclusions:STR-PCR is a sensitive, precise and reliable method for quantitative analysis of hematopoietic chimerism. Selecting sensitive markers to analyze is an economic approach for monitoring of chimerism after transplantation.Sequential and quantitative detection of chimerism may be of great value to predict engraftment, graft rejection, disease relapse and high risk of GVHD.Furthermore it can provide a basis for early intervention of clinical treatment posttransplantation.

GM-CSF secreting leukemia cell vaccinations after allogeneic non-myeloablative peripheral blood stem cell transplantation in patients with advanced myelodysplastic syndrome or refractory acute myeloid leukemia

GM-CSF secreting leukemia cell vaccinations after allogeneic non-myeloablative peripheral blood stem cell transplantation in patients with advanced myelodysplastic syndrome or refractory acute myeloid leukemia

Impact of donor KIR genotype and recipient HLA ligand incompatibility on relapse related mortality and acute graft versus host disease in high-risk patients undergoing haploidentical non-myeloablative peripheral blood stem cell transplants: Differences between lymphoid and myeloid malignancies

Failure to recognize the appropriate HLA class I ligands on the target cell triggers the inhibitory killer Ig-like receptors (KIR) to initiate cytotoxicity and may contribute to graft-vs.-leukemia (GVL) effect. Past studies have shown GVL advantage of the absence (incompatibility) of recipient HLA ligands to donor KIR genes in select patients (pts) undergoing myeloablative transplantation. Here we examine if similar advantage is seen in non-myeloablative transplant (NMT). The KIR-HLA ligand combinations studied were: KIR2DL1-Cw4 (Asn77Lys80); KIR2DL2/3-Cw3 (Ser77Asn80); KIR3DL1-Bw4; and KIR3DL2-A3/A11.

Rapid immune reconstitution and complete donor chimerism after non-myeloablative allogeneic peripheral blood stem cell transplantation (NMSCT) in pediatric patients (PTS) with malignancy

Rapid immune reconstitution and complete donor chimerism after non-myeloablative allogeneic peripheral blood stem cell transplantation (NMSCT) in pediatric patients (PTS) with malignancy

Pulmonary Function Abnormalities 5 Years or More Following Myeloablative and Non-Myeloablative Allogeneic Stem Cell Transplantation for Hematological Disorders - Impact of Chronic GVHD.

Pulmonary function was studied in sixty nine consecutive patients with hematological diseases (65 malignant; 4 benign) 5–12 (median 7.5) years following allogeneic stem cell transplantation from HLA-matched siblings. Fifty-six (81%) patients received total body irradiation-(TBI) based myeloablative bone marrow or peripheral blood stem cell transplantation (MST) for hematological malignancies and 13 (19%) received a fludarabine/cyclophosphamide non-myeloablative peripheral blood stem cell transplantation (NST) for malignant (9) or benign (4) hematological disease. Median age of cohort was 37 years (MST 37, range 10–55; NST 34, range 15–68 years). Thirty nine patients were male. Eleven were smokers. Baseline pulmonary function tests (PFT) showed a median DLCO of 90% predicted (range 59–156%) and FEV1 of 97% predicted (range 64 to132%). Significant pre-transplantation PFT abnormality occurred in 19 (27.5%) patients (DLCO and/or FEV1 <80% of predicted). Twenty five (36%) patients developed acute graft versus host disease (aGVHD) and 43(62%) developed chronic GVHD (cGVHD). At long-term follow-up at a median of 7.5 years after transplant, 32 (42%) patients had PFT abnormalities, 26 with a predominantly restrictive pattern and 6 with a predominantly obstructive pattern. Twenty-two (32%) patients had a mild to moderate decline in PFT (compared with pre-transplant values DLCO/FEV1 value). Of the 32 patients with PFT abnormalities none required supplemental oxygen and only 12 (17.4%) were symptomatic, which included 10 (14.5%) with the most severely depressed pulmonary function (all with predominantly restrictive lung function). In univariate analysis, development of cGVHD (p <0.0001); pre-transplant PFT abnormality (p<0.0001) and a history of smoking (p=0.03); was associated with increased incidence of late PFT abnormality. In multivariate regression analysis, cGVHD (relative risk 36.1; 95% CI 4.1–320) and pre-transplant DLCO/FEV1 of less than 80% of predicted (relative risk 5.5; 95% CI 1.07–29) were independently associated with late decline in PFT. When analyzed for symptomatic PFT abnormality beyond 5 year post-transplant similar results were obtained. The incidence of late PFT abnormality was comparable in both MST (24/56) and NST (5/13) (p=0.51). Our result indicates that a significant proportion of patients developed late PFT abnormality after transplantation, however only a minority are symptomatic. In this series of patients receiving conditioning regimens of different intensity, cGVHD was the only transplant-related risk factor predictive for late pulmonary function defects.

Severe intestinal graft versus host disease after donor lymphocyte infusion; response to extracorporeal photochemotherapy

We present a patient with acute myelogenous leukemia who developed severe acute intestinal graft versus host disease (GVHD) after donor lymphocyte infusion (DLI) following non-myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBCT). One month after DLI, patient developed severe abdominal cramps, watery diarrhea without any signs or symptoms of the skin and liver GVHD. Treatment with steroid, cyclosporine A, tacrolimus and mycophenolat mofetil were not effective in controlling intestinal symptoms. Extracorporeal photochemotherapy (ECP), a recently used procedure in the treatment of GVHD was employed periodically and the symptoms subsided gradually. Acute GVHD after DLI may occur severely and atypically, but being limited to the intestine has rarely been reported.

Nonmyeloablative peripheral blood stem cell transplant for T-cell prolymphocytic leukaemia complicated by fulminant haemolysis and acute renal failure at engraftment secondary to minor ABO incompatibility

We present a 54-year-old man who underwent human leucocyte antigen-identical sibling nonmyeloablative peripheral blood stem cell transplant for primary refractory T-cell prolymphocytic leukaemia (T-PLL). His clinical course was complicated by fulminant haemolysis and acute renal failure at the time of engraftment because of minor ABO incompatibility between the donor and the recipient. This case highlights the curative potential of nonmyeloablative transplantation for T-PLL as well as the potential severity of immune haemolysis secondary to minor ABO incompatibility.

Non‐myeloablative allogenic peripheral blood stem cell transplantation in a patient with refractory osteosarcoma

The prognosis of patients with relapsed osteosarcoma is dismal despite the use of intensive chemotherapy. We describe a patient with refractory osteosarcoma who underwent non-myeloablative peripheral blood stem cell transplantation (PBSCT) from an human leukocyte antigen (HLA)-identical sibling during a third complete remission. The patient suffered pulmonary relapse after the transplantation. Cyclosporin A withdrawal induced a graft-vs.-osteosarcoma effect and graft-vs.-host disease, but eventually the tumor progressed. Although our experience in this case suggested the presence of a graft-vs.-osteosarcoma effect during non-myeloablative allogenic PBSCT, this strategy might have limited value for refractory osteosarcoma with rapid growth kinetics.

Tc-99m MDP bone scintigraphy of myositis as a manifestation of chronic graft-versus-host disease after non-myeloablative peripheral stem cell transplantation

A 27-year-old man developed polymyositis as a manifestation of chronic graft-versus-host disease (GVHD) after non-myeloablative peripheral blood stem cell transplantation (PBSCT). Bone scintigraphy showed intense, striped, and heterogeneous accumulation of Tc-99m methylene diphosphonate (MDP) in the soft-tissue of his lower limbs, while faint activities were seen in the right upper limb. Tc-99m MDP scintigraphy was very useful for accurate and objective evaluation of the severity of the muscle injury and the extent of polymyositis caused by chronic GVHD.

Health-related quality of life and symptom distress in patients undergoing non-myeloablative (NST) versus myeloablative (MT) allogeneic peripheral blood stem cell transplantation (PBSCT)

Health-related quality of life and symptom distress in patients undergoing non-myeloablative (NST) versus myeloablative (MT) allogeneic peripheral blood stem cell transplantation (PBSCT)

Massive Immune Hemolysis After Non-myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation with Minor ABO-incompatibility

A 35-year-old male, blood group B, Rh(D)+ type, received an allogeneic peripheral blood stem cell (PBSC) transplant after a non-myeloablative regimen of fludarabine and cyclophosphamide for resistant γ δ cutaneous T-cell lymphoma (CTCL). The donor was his HLA-identical brother, blood group O, Rh(D)+ type. Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporine alone. On day +8, massive immune hemolysis occurred, followed by acute renal failure. Hemodialysis was performed eight times until recovery of renal function on day +24. The risk of delayed immune hemolysis after non-myeloablative allogeneic PBSC transplantation with minor ABO-incompatibility must be considered.

Non-myeloablative allografting from human leucocyte antigen-identical sibling donors for treatment of acute myeloid leukaemia in first complete remission.

Many patients with acute myeloid leukaemia (AML) in first complete remission (CR1) are ineligible for allogeneic transplantation as a result of age or medical problems other than leukaemia. Eighteen patients (median age 59 years, range 36-73 years) with de novo (n = 13) and secondary (n = 5) AML in morphological CR1, who were not candidates for conventional allografting, received non-myeloablative peripheral blood stem cell transplants from human leucocyte antigen identical sibling donors after conditioning with 2 Gy total body irradiation (TBI; n = 10) or 2 Gy TBI and 90 mg/m2 of fludarabine (n = 8). Postgrafting immunosuppression was with cyclosporine and mycophenolate mofetil. Two rejections were observed in patients not given fludarabine and one died with relapse. Overall, 10 patients died between 77 and 841 d, seven from relapse and three from non-relapse mortality (NRM). Day +100 NRM was 0% with a 1-year estimated NRM of 17%[95% confidence interval (CI) 0-35%]. The median follow-up among the eight survivors was 766 d (range, 188-1141 d). Seven of these eight survivors remain in complete remission (CR). One-year estimates of overall and progression-free survivals were 54% (95% CI 31-78%) and 42% (95% CI 19-66%) respectively. While follow-up is short, this analysis demonstrates that the procedure is sufficiently safe to be studied in a wider group of patients.