Interferon-α salvage treatment is effective for patients with acute leukemia/myelodysplastic syndrome with unsatisfactory response to minimal residual disease-directed donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation / 医学前沿

The efficacy of salvage interferon-α (IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI) (n = 24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2-3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and > 2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.

Successful treatment of post-transplant relapsed acute myeloid leukemia with FLT3 internal tandem duplication using the combination of induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Report of three cases / Tratamento bem-sucedido de leucemia mieloide aguda recorrente após transplante com duplicação interna em tandem FLT3 usando combinação de indução por quimioterapia, infusão de linfócitos de doador, soferanib e azacitidina. Relato de três casos

ABSTRACT Acute myeloid leukemia is a hematopoietic stem cell neoplastic disease associated with high morbidity and mortality. The presence of FLT3 internal tandem duplication mutations leads to high rates of relapse and decreased overall survival. Patients with FLT3 internal tandem duplication are normally treated with hematopoietic stem cell transplantation in first complete remission. Nevertheless, the incidence of post-transplant relapse is considerable in this group of patients, and the management of this clinical condition is challenging. The report describes the outcomes of patients with FLT3 internal tandem duplication positive acute myeloid leukemia who relapsed after allogeneic hematopoietic stem cell transplantation and were treated with the combination of re-induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Three cases are described and all patients achieved prolonged complete remission with the combined therapy. The combination of induction chemotherapy followed by donor lymphocyte infusion, and the maintenance with azacitidine and sorafenib can be effective approaches in the treatment of post-hematopoietic stem cell transplant and relapsed FLT3 internal tandem duplication positive acute myeloid leukemia patients. This strategy should be further explored in the context of clinical trials.

RESUMO A leucemia mieloide aguda é uma doença neoplásica de células-tronco hematopoiéticas com alta morbimortalidade. A presença de mutações de duplicação em tandem de FLT3 leva a altas taxas de recorrência e a menor sobrevida global. Os pacientes com duplicação em tandem de FLT3 são normalmente tratados com transplante de células-tronco hematopoiéticas na primeira remissão completa. No entanto, a incidência de recidiva pós-transplante é considerável neste grupo de pacientes, e a conduta, nestes casos, é um desafio. O relato descreve os resultados do tratamento de pacientes com leucemia mieloide aguda positiva e duplicação em tandem de FLT3 que recidivaram depois do transplante alogênico de células-tronco hematopoiéticas e que foram tratados com combinação de quimioterapia de reindução, infusão de linfócitos de doador, sorafenib e azacitidina. São descritos três casos, e todos os pacientes apresentaram remissão completa prolongada com a terapia combinada. A combinação de quimioterapia de indução, seguida de infusão de linfócitos do doador, e a manutenção com azacitidina e sorafenib podem ser abordagens eficazes no tratamento da recorrência pós-transplante em pacientes com leucemia mieloide aguda e duplicação em tandem de FLT3. Essa estratégia deve ser mais explorada no contexto de ensaios clínicos.

A study of the Unna Boot compared with the elastic bandage in venous ulcers: a randomized clinical trial / Estudo da Bota de Unna comparado à bandagem elástica em úlceras venosas: ensaio clínico randomizado / Estudio de la Bota de Unna comparada al vendaje elástico en úlceras venosas: ensayo clínico aleatorio

AbstractObjective: to analyze the process of tissue repair in patients with venous ulcers using inelastic compression therapy (the Unna Boot), in comparison with the use of the elastic bandage.Method: a controlled randomized clinical trial in which the patients (n=18) were allocated to two groups, those who used the Unna Boot (group B) and those who used the elastic bandage (group A). The study's follow-up period was 13 weeks.Results: a significant reduction took place, at the level of 5%, in the area, in square centimeters, of the ulcers of group B (p<0.0001) throughout the treatment, and there was a tendency of group A for reduction in the area of the ulcer, in centimeters squared (p=0.06), only after the fifth week.Conclusion: the treatment with the Unna Boot presented better results in venous ulcers with areas over 10cm², and the elastic bandage with Petrolatum(r) gauze in venous ulcers below 10cm². Brazilian Clinical Trials Register: Trial (req: 195) and WHO UTN U1111-1122-5489.

ResumoObjetivo:analisar o processo de reparo tecidual de pacientes com úlcera venosa em uso da terapia compressiva inelástica (Bota de Unna), em comparação ao uso da bandagem elástica.Método:ensaio clínico controlado randomizado em que os pacientes (n=18) foram alocados em dois grupos, os que utilizavam a Bota de Unna (grupo B) e os que utilizavam a atadura elástica (grupo A). O tempo de seguimento da pesquisa foi de treze semanas.Resultados:ocorreu redução significativa, no nível de 5%, na área, em centímetros quadrados, das úlceras do grupo B (p<0,0001) ao longo de todo o tratamento, e tendência do grupo A à redução, na área da úlcera, em centímetros quadrados (p=0,06), apenas após a quinta semana.Conclusão:o tratamento com a Bota de Unna apresentou melhor resultado em úlceras venosas com áreas superiores a 10cm², e a atadura elástica com a gaze Petrolatum(r)em úlceras venosas inferiores a 10cm². Registro Brasileiro de Ensaios Clínicos: Trial (req: 195) e WHO UTN U1111-1122-5489.

ResumenObjetivo:analizar el proceso de reparación del tejido de pacientes con úlcera venosa que usan la terapia compresiva inelástica (Bota de Unna), en comparación con el uso del vendaje elástico.Método:ensayo clínico controlado aleatorio en que los pacientes (n=18) fueron designados en dos grupos, los que utilizaban la Bota de Unna (grupo B) y los que utilizaban el vendaje elástico (grupo A). El tiempo de duración de la investigación fue de trece semanas.Resultados:se constató reducción significativa, al nivel de 5%, en el área, en centímetros cuadrados, de las úlceras del grupo B (p<0,0001) a lo largo de todo el tratamiento; y tendencia del grupo A a la reducción, en el área de la úlcera, en centímetros cuadrados (p=0,06), solamente después de la quinta semana.Conclusión:el tratamiento con la Bota de Unna presentó mejor resultado en úlceras venosas con áreas superiores a 10cm², y el vendaje elástico con la gasa Petrolatum(r)en úlceras venosas inferiores a 10cm². Registro Brasileño de Ensayos Clínicos: Trial (req: 195) y WHO UTN U1111-1122-5489.

Efficacy of Donor Lymphocyte Infusion for Treating Relapsed High-Risk Leukemia patients after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of donor lymphocyte infusion (DLI) for treating relapsed high-risk leukemia patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The data of 15 leukemia patients who had received DLI and 13 leukemia patients who had not received DLI in Zhujiang Hospital from 2000 to 2014 were studied retrospectively, and their 1 and 3 year overall survival rate (OS) were compared between the two groups.</p><p><b>RESULTS</b>In 15 patients received DLI, the 1 and 3 year OS were 58.3% and 46.7%, the 1 and 3 year disease-free survival (DFS) were 22.0% and 11.0%, respectively. The main death cause in these patients included relapse (n = 5) and acute GVHD (n = 1), whereas in 13 patients who had not received DLI, the 1 and 3 year OS were 29.9% and 15.0% respectively, their 1 year DFS were 11.2%. The main death cause in these patients were relapse (n = 9). The 1 and 3 year OS of patients who had received DLI was higher as compared with the patients who had not received DLI. but this difference was no statistically significant (P = 0.069).</p><p><b>CONCLUSION</b>DLI is an effective method for treating patients with relapsed leukemia, and may improve the therapeutic efficacy of DLI by combining other methods or alternating the types of the donor lymphocytes.</p>

Aborto recurrente de etiología aloinmune / Alloimmune recurrent spontaneous abortion

Los mecanismos que subyacen la reproducción humana son muy complejos, por lo que cualquier pérdida gestacional implica el tener que considerar diversas etiologías, más aun si se trata de pérdidas gestacionales recurrentes dentro de las que la inmunidad juega un papel especialmente importante. Desde hace varias décadas, el factor aloinmune ha sido reconocido como un desencadenante frecuente de la interrupción del embarazo, haciéndose de esta forma relevante su estudio en mujeres con aborto recurrente. En el presente artículo, a partir de una búsqueda sistemática de información, se revisan con detalle los aspectos relacionados con la fisiopatología, el diagnóstico y el tratamiento del aborto recurrente de etiología aloinmune, buscando con esto sensibilizar al profesional de la salud sobre su consideración ante una mujer con pérdida recurrente de la gestación.

The mechanisms underlying the human reproduction are very complex, so any pregnancy loss implies the need of considering various etiologies, even more if those pregnancy losses are recurrent within which the immunity plays an important role. Since decades, the alloimmune factor has been recognized as a frequent trigger of the pregnancy interruption, thus becoming relevant its study in women with recurrent miscarriage. In the present article, through a systematic search of information, details concerning to the physiopathology, diagnosis and treatment of the recurrent miscarriage of alloimmune etiology are reviewed, looking to sensitize the health professional about its consideration when evaluating a woman with recurrent pregnancy loss.

Effect of pretreatment with apoptotic donor spleen cells on spleen lymphocyte function of recipient rats after islet transplantation / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of pretreatment with apoptotic donor spleen cells on spleen lymphocyte function of recipient rats undergoing islet transplantation to explore new approaches to prolong islet graft survival.</p><p><b>METHODS</b>Apoptotic spleen cells from donor rats were obtained by exposure to γ-ray irradiation from (60)Co. Diabetic SD rat models were randomly divided into 4 groups to receive tail vein injections with saline (group A), normal cells (group B), apoptotic donor cells (group C), or necrotic donor cells (group D). One week later, orthotopic transplantation of islets under the renal capsule was performed. Before and at 1 and 2 weeks after islet transplantation, the recipient rats were examined for proliferative activity of spleen lymphocytes with CFSE cell staining and for IL-2 and IL-10 expressions in the cells using ELISA.</p><p><b>RESULTS</b>Pretreatment with donor apoptotic cells significantly suppressed the proliferative activity of recipient spleen lymphocytes before and at 1 and 2 weeks after islet transplantation as compared with the other three groups (P<0.05). The level of IL-2 was significantly decreased while IL-10 increased in apoptotic donor cell pretreatment group compared with those in the other 3 groups at each time point of observation.</p><p><b>CONCLUSION</b>The effect of pretreatment with apoptotic donor cells on recipient spleen lymphocytes suggest an important role of apoptotic donor spleen cells in immune tolerance of grafts.</p>

Prophylactic G-CSF mobilized donor lymphocytes infusion after non-myeloablative stem cell transplantation prevents relapse in patients with high-risk leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the anti-leukemia effects of prophylactic G-CSF mobilized donor lymphocytes infusion (pG-DLI) and its relationship with the incidence of graft-versus-host disease (GVHD) in high-risk leukemia patients with non-myeloablative stem cell transplantation (NST).</p><p><b>METHODS</b>12 patients with high-risk leukemia were analyzed, including Ph⁺ acute lymphocytic leukemia (n=1), acute leukemia (AL) with persistent non-complete remission (n=2), acute myeloid leukemia (AML) with central nervous system (CNS) relapse (n=3), hybrid AL (n=1), secondary AML evolving from myelodysplastic syndrome (MDS/AML) (n=2), chronic myeloid leukemia in accelerated phase (CML-AP) (n=1), CML in blastic phase (CML-BP) (n=2). All patients received non-myeloablative conditioning and pG-DLIs were administered 30-40 days post transplantation if no signs of GVHD were present. The percentage of donor cell chimera was analyzed by short tandem repeat-polymerase chain reaction (STR-PCR) just before and after pG-DLI. The incidence of leukemia relapse and GVHD were observed.</p><p><b>RESULTS</b>12 high-risk leukemia patients with a median age of 38 (range: 29-52) years received G-DLI at a median interval of 35 (32-40) days. The median numbers of infused mononuclear cells (MNCs), CD34⁺, and CD3⁺ cells/kg recipient body weight was 2.3×10⁸/kg, 1.7×10⁶/kg, and 0.6×10⁸/kg, respectively. 10 of 12 patients had full donor chimera before pG-DLIs and conversion from mixed to full donor chimera occurred in the other 2 patients shortly after pG-DLI. Grade II acute GVHD (aGVHD) was observed in only 2 patients and chronic GVHD (cGVHD) developed in 6 patients, including involvement of skin (n=3), skin and intestine (n=2), liver (n=1). 1 patient died of cGVHD. With a median follow-up of 40 (24-64) months, 7 patients are alive in remission, with 3-year actuarial overall survival (OS) and disease-free survival (DFS) rates of the same 58.3%.</p><p><b>CONCLUSION</b>Our findings indicate that pG-DLI after NST does not increase the risk of aGVHD, but could enhance the capacity graft-vs-leukemia and prevent relapse in high-risk leukemia patients.</p>

Role of chimerism monitoring and donor lymphocyte infusion in eliminating the risk of graft rejection following HSCT in thalassemia patients-review / 中国实验血液学杂志

One of the major obstacle for hematopoietic stem cell transplantation (HSCT) to treat patients with beta-thalassemia is graft rejection (GR). The proportion of donor-derived cells continually declined in mixed chimerism (MC), finally leading to graft failure. Monitoring chimerism after transplant consecutively can early find unstable mixed chimerism and rejection, which provide the basis for donor lymphocyte infusion (DLI); for imminent risk of graft rejection, escalating doses of DLI is a feasible method for converting unstable MC towards stable MC or full donor chimerism. This review focuses on advancement of chimerism monitoring and DLI after HSCT for patients with β-thalassemia major.

Clinical efficacy of decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen on elderly patients with high risk myelodysplastic syndrome and acute myeloid leukemia / 中国实验血液学杂志

This study was aimed to observe the clinical efficacy and adverse effects of decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen on elderly patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Five elderly patients with MDS and AML were treated with decitabine plus improved CAG chemotherapy and donor peripheral lymphocyte infusion regimen. Examinations on liver and renal function, electrocardiogram and bone marrow analysis were performed before and after treatment, and adverse effects were observed. The results indicated that after a course of treatment by decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen, the total effective rate was 100%, and 4 patients (80%) achieved complete remission, 1 patient achieved partial remission. The dominant clinical adverse effect was bone marrow depression, the median time of neutrophil>0.5×10(9)/L and platelet>20×10(9)/L was 15 d and 16 d respectively for patients without previous MDS. It is concluded that decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen may be effective with less adverse effects for elderly primary AML and high risk MDS patients, it is a promising therapeutic methods and worthy to deeply study.

Treatment of leukemia with immunized donor cell infusion after nonmyeloablative haploidentical bone marrow transplantation / 中国实验血液学杂志

This study was purposed to investigate the therapeutic effects of early transfusion of immunized donor lymphocytes after haploidentical transplantation by means of mouse model of nonmyeloablative haploidentical bone marrow transplantation. CB6F1 female mouse was served as recipient and C57BL/6 male mouse was served as donor. Each CB6F1 female mouse was subjected to intravenous transfusion with 1×10(6) erythroleukemia (EL9611) cells at day 4 before transplantation, followed with intraperitoneal injection of Ara-C (0.015 g) respectively at day 2 and day 1, then conditioned for BMT with TBI (450 cGy) at day 1 before transplantation. After conditioning (day 0), each of recipients was transplanted with 6×10(7) mixture of bone marrow and spleen cells from the C57BL/6 mice, and was infused with 6 × 10(7) immunized donor lymphocytes at day 15 after transplantation. All treated animals were evaluated for survival, development of leukemia and aGVHD. The donor CD3(+) cell chimerism and sex determining region Y gene (SRY)in recipients were monitored periodically after transplantation. The results showed tht all mice with only inoculation of 10(6) EL9611 cells survived for 15 ± 1 days (n = 4); all mice of other groups obtained the varying degrees of implantation. SRY could be detected at day 30 and 60 after transplantation. The chimerism of donor CD3(+) cells in mixed bone marrow transplantation (MT) group at day 14, 30 and 60 respectively reached 17.95% ± 12.03%, 37.34% ± 2.78% and 47.06% ± 6.1%. In donor lymphocyte infusion (DLI) group it reached 69.78% ± 12.62%, 75% ± 15.97%, 83.41% ± 16.07% at day 30, 45 and 60 after transplantation. The mice of MT and DLI group survived for 66.66 ± 1.47 days and 78.2 ± 7.82 days. It is concluded that the high tumor burden before transplantation can affect donor cell engraftment and prognosis.Early post-transplanted infusion of immunized lymphocytes from donor can help to improve the therapeutic efficacy and survival.

Clinical study of autologous cytokine induced killer cell infusion treating for elderly patients with myelodysplastic syndrome / 中国实验血液学杂志

Objective of this study was to evaluate the effectiveness and safety of autologous cytokine induced killer (CIK) cells combined with IL-2 in treatment of elderly patients with myelodysplastic syndromes (MDS). Peripheral blood mononuclear cells were isolated from 6 elderly MDS patients and were stimulated by cytokines in vitro to form CIK cells. The autologous CIK cells were then infused back into the corresponding patients. The regimen was repeated every 4 weeks. Effector cell proportion changes, adverse effects, effects on inflammation, hemoglobin level and blood transfusion were assessed after treatment. The results showed that after autologous CIK cell infusion, the percentages of CD3(+), CD3(+)CD8(+) and CD3(+)CD56(+) increased significantly (p < 0.05). No severe adverse effects were observed in all patients. It also significantly reduced inflammation frequency and shortened high fever duration. During stable stage of disease, the CIK cell infusion could reduce the red blood cell infusion amount and stabilize hemoglobin level. However, the natural course of transformation from myelodysplastic syndromes to high-risk subtypes could not be changed by CIK cell treatment. It is concluded that the autologous CIK cell infusion is a safe and effective therapy for geriatric myelodysplastic syndrome.

Impact of transfusion of apoptotic and necrotic thymocytes on the survival of mice with sepsis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of transfusion of apoptotic and necrotic thymocytes prior to sepsis on the survival rate of mice.</p><p><b>METHODS</b>BALB/c mice are divided into 3 groups and received intravenous injection of PBS (control), apoptotic thymocytes, or necrotic thymocytes. Three days later, cecal ligation and puncture (CLP) were performed to induce sepsis in these mice, and their survival and organ damage were observed.</p><p><b>RESULTS</b>The survival rates of mice in PBS group was 44.6% at the end of first week after CLP, and obvious lung and kidney damages were observed. A significant increase in the survival rate was found in apoptotic cell transfusion group (69.6%, P=0.012), with also lessened lung and kidney damages. The survival rate of mice in necrotic cell transfusion group was only 31.6% at 2 weeks, significantly lower than that in PBS group (P=0.035), and the lung and kidney damage was even more obvious.</p><p><b>CONCLUSION</b>Transfusion of apoptotic thymocytes 3 days before induction of sepsis can reduce organ damage and improve the survival rate of mice, while necrotic cell transfusion produces the opposite effect.</p>

Relapsed diffuse large B-cell lymphoma treated by reduced-intensity allogeneic stem cell transplantation with donor lymphocyte infusion

A 42 years old male with relapsed diffuse large B-cell lymphoma was given second-line chemotherapy followed by reduced intensity allogeneic stem cell transplantation from HLA matched brother. Twelve weeks posttransplant, his disease relapsed evidenced by the appearance of lymphoma cells in the peripheral blood and declining donor chimerism. Donor lymphocyte infusion was given that induced complete lymphoma remission. The patient is well 3 years posttransplant with his disease in complete remission

Clinical study of allogeneic hematopoietic stem cell transplantation for relapsed/refractory acute lymphocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy and toxicity of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for relapsed/refractory acute lymphocytic leukemia (ALL).</p><p><b>METHODS</b>Forty-seven patients with relapsed/refractory ALL received allo-HSCT, which containing 19/47 from HLA-identical sibling donors (sib-HSCT), 18/47 from HLA-identical unrelated donors (URD-HSCT) and 10/47 from haplo-identical donors (Hi-HSCT). Conditioning regimens included "TBI plus Cyclophosphamide (Cy) (42/ 47)" or "busulfan (Bu) plus Cy (5/47)". Cyclosporine (CsA) combined with a short-course Methotrexate (MTX) were used for graft versus host disease (GVHD) prophylaxis. In addition, patients receiving URD-HSCT or Hi-HSCT were given mycophenolate mofetil (MMF) and anti-thymocyte immunoglobulin (ATG). Patients with molecular or cytogenetic relapse tendency on minimal residual disease (MRD) monitoring received donor lymphocyte infusion (DLI).</p><p><b>RESULTS</b>All patients tolerated the therapy well except for mucositis. Renal dysfunction occurred in 2 patients on CsA therapy. Epilepsy occurred in 1 patient, fatal infectious complications in 9 (including 3 interstitial pneumonia), grade III-IV acute GVHD (aGVHD) in 7, chronic GVHD (cGVHD) in 22 and hemorrhagic cystitis (HC) in 4 patients. Thirteen patients relapsed after transplantation. The median time of hematopoietic reconstitution was + 17 ds. Nineteen patients received DLI, and 6 of them had no disease progression. With a median follow-up duration of 43 (10-77) months, the estimated 5-year overall survival (OS) and disease free survival (DFS) rates were 49.65% and 46.55%, respectively.</p><p><b>CONCLUSION</b>Allo-HSCT is an effective therapy for relapsed/refractory ALL. Relapse after transplantation, fatal infection, and severe acute GVHD are the main causes for failure. DLI might decrease the relapse rate after transplantation.</p>

The action of donor-derived NK cell in leukemic mice MHC haplotype-mismatched bone marrow transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the role of donor-derived NK cells in haploidentical bone marrow transplantation (BMT) in leukemic mice.</p><p><b>METHODS</b>CB6F1(H-2b/d) mice model of EL9611 (H-2d) erythroleukemia was established by injection of EL9611 (H-2d) cells via tail vein. CB6F1(H-2b/d) mice were used as recipient, and C57BL/6(H-2b) mice as donor. Five days later, 70 CB6F1(H-2b/d) mice were randomly divided into 7 groups (10 mice per group) as follows: group 1: without treatment; group 2: simple-irradiated group; group 3: treated with cytarabine (Ara-C) at 50 mg/kg x6 d; group 4: simple BMT; group 5: haploidentical BMT with graft-versus-host disease (GVHD) that injected with bone marrow cells and spleen cells of C57BL/6(H-2b) mice 4 hours after irradiation; group 6: after irradiated with 9 Gy, mice were injected with C57BL/6(H-2b) NK cells (1 x 10(6)) and 4 hours later with BM cells, group 7: after irradiation of 9 Gy, mice were injected with C57BL/6(H-2b) NK cells (1 x 10(6)) and 4 hours later with BM cells and spleen cells. The blood routine test, survival time, body weight, and histopathology in the recipients were observed and compared among these group.</p><p><b>RESULTS</b>The survival time was (10.1 +/- 0.9), (9.8 +/- 0.9), (22.7 +/- 3.2) and (20.1 +/- 1.7) days in groups 1, 2, 3, and 5 respectively; was (30.1 +/- 16.0) days in group 4, out of which 2 mice survived for more than 30 days. The survival time was (39.1 +/- 18.1) and (49.3 +/- 17.2) days in groups 6 and 7 respectively, out of which 4 mice in group 6 and 7 mice in group 7 survived for more than 30 days. The survival time in group 6 was much longer than that in group 1, 2, 3 and 5 (P < 0.01). The survival time in group 7 was much longer than that in other groups (P < 0.05). The liver and spleen enlargement, organ destruction and infiltration with leukemic cells were observed in mice died from leukemia. The chimerism of Y chromosome appeared (80%-90%) in long-term survival mice in groups 6 and 7.</p><p><b>CONCLUSION</b>Donor-derived NK cells have the antileukemia ability and reduce GVHD in haploidentical BMT in erythroleukemia mice (EL9611, H-2d).</p>

Alloreactive NK cells enhance the effect of donor lymphocyte infusion in the management of relapsed lung cancer after haploidentical hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was aimed to study the potential effects of alloreactive NK cells (allo-NKs) in therapy of relapsed lung cancer after haploidentical hematopoietic stem cell transplantation using donor lymphocyte infusion (DLI). The F1 donors derived-NK cells were purified with MACS magnetic separation system, in which the proportion of the alloreactive Ly49A(+) cells was detected by flowcytometry and alloreactivity was measured by LDH method. The relapse model of lung cancer after haploidentical-HSCT was established. The distribution kinetic of infused donor lymphocytes in vivo was analyzed. The inhibition of relapse tumor, infiltration of lymphocytes in situ and fluctuation of 22 kinds of cytokines in serum after DLI were compared among different groups. The results showed that the infused donor cells of allo-NK group were accumulated mostly in lung, spleen and kidney for more than 48 hours with considerable higher levels according to the distribution kinetic curve. The sizes of relapse tumors between chemotherapy + PBS group and chemotherapy + DLI group showed no difference. However, the relapsed tumors in allo-NK + DLI group were significantly smaller than that in chemotherapy + DLI group or allo-NK + PBS group, in which increased infiltration of lymphocytes were defined in situ. The levels of cytokines such as MCP-1, IL-17, IL-12 and MCP-5 in serum of allo-NK + DLI group ascended compared with control group, though the level of IL-10 declined simultaneously. It is concluded that allo-NKs prolong the survival time of infused donor lymphocytes in vivo, promote the secretion of inflammatory cytokines and Th1-type of cytokines, and further improve the antitumor effects of DLI against relapse after transplantation.

Establishment of a bone marrow failure mouse model by immune injury / 中华血液学杂志

<p><b>OBJECTIVE</b>To establish a mouse model for the study of pathophysiologic mechanism and treatment of bone marrow failure (BMF).</p><p><b>METHODS</b>Balb/c mice (recipient) were irradiated 5.0 Gy by gamma rays of (60)Co, and then infused 5 x 10(6) lymph node (LN) cells from DBA/2 mice (donor) in 4 hours. Pancytopenia was monitored by cell counting, bone marrow damage was assessed by histological staining and mononuclear cell counting. Serum IFN-gamma concentration was measured by ELISA. The proportion of Treg in spleen was detected by flow cytometry.</p><p><b>RESULTS</b>Irradiation and infusion of LN cells led to rapid development of severe pancytopenia and BM hypoplasia, which reached the most severity at d14. The pancytopenia remained at d28 and displayed no signs of recovery. The bone marrow was full of adipose cells with scarcity of hematopoietic cells at d14 and persisted at least for 28 days, being similar to the feature of aplastic anemia. Serum IFN-gamma concentration was 6.3 fold increased \[(170.0 +/- 17.0) vs (27.7 +/- 7.1) pg/ml\] at d6. Tregs were decreased after infusion, and then increased \[(3.38 +/- 0.52)%\] and recovered to normal \[(4.04 +/- 0.44)%\] at d21. The expression level of the specific transcription factor Foxp3 was similar to normal.</p><p><b>CONCLUSION</b>The MHC antigen of Balb/c mice is identical to that of DBA/2 mice, but their minor antigen differs. 5.0 Gy irradiation and then 5 x 10(6) lymphocyte infusion can induce BMF similar to the features of aplastic anemia.</p>

Influence of intra-bone marrow infusion of donor lymphocytes on development of graft-versus-host disease and level of IL-4 and IFN-gamma in peripheral blood / 中国实验血液学杂志

To investigate the effect of donor lymphocyte infusion (DLI) by intra-bone marrow (IBM) routes on the incidence of graft-versus-host disease(GVHD), level of IL-4 and IFN-gamma after allogeneic peripheral hematopoietic stem cell transplantation (allo-PBSCT). Female C57BL/6 mice as recipients received total body irradiation (TBI) on day 0, followed by injection of peripheral hematopoietic stem cells from mobilized donor of male BALB/c with the granulocyte-colony stimulating factor (rhG-CSF), and DLI was performed via ether IV or IBM routes. The severity of GVHD was compared in recipients received allogeneic IBM-DLI with those mice received IV-DLI; at 14 days after DLI, the levels of IL-4 and interferon (IFN)-gamma were tested by ELISA. The results showed that as compared with IV-DLI group the frequency and severity of GVHD were reduced in IBM-DLI (p < 0.01); the level of IL-4 significantly increased, while the level of IFN-gamma decreased in group IV-DLI (p < 0.01). It is concluded that IBM-DLI declines the incidence and severity of GVHD after allo-PBSCT.