Double transplant successful treatment of 1 case of severe regenerative anemia

Aplastic anemia (aplastic anemia, AA) is a bone marrow failure disease caused by physical, chemical and biological factors, clinically characterized by anemia? Bleeding? Infection? Heavy regenerative anemia (SAA) and extremely heavy regenerative anemia (VSAA) mortality rate is high, a serious threat to the life of patients? Method1?For patients over 40 years of age, intensive immunosuppressive therapy can also be chosen, but compared with MSD-HSCT, low efficiency and high recurrence rate? Therefore, most hospitals currently recommend MSD-HSCT to treat SAA or VSAA patients over 40 years of age? Due to the serious adverse reactions of its compatriots in the peripheral blood stem cell collection process, forced to suspend peripheral blood stem cell collection, the collection of bone marrow and peripheral blood CD34 plus cell number can not meet the stem cell implantation requirements? In order to promote stem cell implantation, avoid implant failure or adverse risk, save the patient's life, we in the patient infusion donor peripheral hematopoionstem stem cell after The next day, for patients to jointly intake a HLA type 9/10 conjoined non-blood cord blood stem cells for double transplantation? Double transplantation enables patients to successfully obtain hematopoietic reconstruction, the onset of disease is alleviated, no acute and chronic transplantanti-host disease occurred, to April 2018 no disease survival, is the report as follows?1 case data1.1 medical history introduction Patient, male, 43 years old, since January 2017 appeared fingers and other parts of the skin damage after bleeding can not stop, in May 2017 there was a physical decline? Progressive dizziness and fatigue, then to the local hospital, proposed "full blood" Cell reduction "treatment? No fever, no nausea? Vomiting? Abdominal pain and diarrhea, no cough? coughing sputum, no headache and blurred visuals? Physical examination: body temperature 36.2 degrees C, clear mind, severe anemia, whole body skin mucosa does not see yellow dye, visible spots? Spots, shallow lymph nodes did not touch the swelling; neck soft, tracheosary center, chest clamore pain negative, double lung breathing sound clear, unheard and wet sound; heart rhythm, valve hearing area unheard and pathological murmurs; abdominal flat soft, liver and spleen under the ribs Not, nervous system test did not lead to positive signs? Auxiliary test: blood routine: white blood cell 0.4 x 109/L, absolute number of neutrophils 0.2 x 109/L, lymphocyte percentage 52.3%, hemoglobin 41g/L, Net-woven red blood cells 0.016 x 1012/L, platelets 6 x 109/L; peripheral blood Flaer test negative; right tibia bone marrow image prompts bone marrow hyperploff reduction, granularity reduction, platelet reduction; thoracic bone marrow like-to-be suggested bone marrow hyperplout, platelet reduction, particle line ratio significantly reduced? Puncture dysphonic tissue, hematopoietic tissue capacity of 15 to 20VOL, showed low growth of bone marrow tissue; granulation red ratio is basically normal; granule precursor cells are small, late and below stage splintered in the distribution; red lines are mainly in the middle and late infant stages, the number is reduced; macronuclear cells are lacking, interstitial lymphocytes and plasma cells are scattered in the distribution (Figure 1)?1.2 Treatment after patient and compatriot second sister HLA high-resolution type 10/10 combination? In June 2017 for patients to carry out MSD-HSCT, pretreatment program is: cyclophosphamide 50mg kg-1?d-d-1,-5d-2d (0days with infusion stem cells on the day, negative before transplant, positive after transplant); rabbit source anti-thymus cell immunoglobulin 3.5mg kg-1-d-1, -5d-2d? On July 4, 2017, the total nuclear cell (TNC) count of the bone marrow collection of the infusion donor was approximately 2.8 x 108/kg (subject weight), and the CD34 plus cells were 0.27 x 106/kg (recipient weight) July 5 as planned to infuse the peripheral hematopoietic stem cells after the mobilization of the donor? Because the donor in the peripheral blood stem cell collection process panic? Chest tightness? chest compression feeling? Limbs numb, can not tolerate peripheral blood stem cell collection, forced to terminate the collection early? The TNC of the peripheral blood collection collected was 6.433 x 108/kg (subject weight), the number of cells cd34 was 0.77 x 106/kg (the recipient's weight), the cell vitality was 100%? TNC is 9.233 x 108/kg (subject weight)? The number of hematopoietic stem cells in the patient's infusion of compatriots theoretically does not meet the requirements of the patient's hematopoietic stem cell implantation, and then on July 6, 2017, the patient infusion non-blood umbilical cord Blood one, HLA high-resolution match inglision is 9/10, male, blood type B plus, from Shanghai umbilical blood bank, infusion of cord blood stem cells TNC is 2.44 x 107/kg (recipient weight)? The number of CELLS of CD34 plus is 1.44 x 105/kg (the recipient's weight), cell vitality is 90%? Patients in stem cell infusion after the s29d to obtain neutrophil implantation, after transplantation of the red line implant, after transplantation of the 17d hematopoietic implantation, hematopoietic stabilization reconstruction, after transplanting the bone marrow to review the primary disease mitigation?1.3 Complications Pneumonia Krebsaxaxandaandemia and abscess espertin in the course of transplant treatment, after active treatment, the infection was controlled? After transplantation, eBV emis, after transplantation, after 2 months of shallow lymph nodes, liver and spleen swelling, clinical consultation: After transplantation of lymphocyte proliferation disease, given 1 per week infusion of rituximatox (375mg m-2-1), and the withdrawal of immunosuppressants, after 4 weeks of continuous treatment, the enlarged lymph nodes shrink, liver spleen shrinkage, monitoring the number of EB virus copies is normal? 1.4 Implant Monitoring Patient STR-PCR after transplant ation100% for compatriot donor sources, after transplant ingestion of 1 month?2 months bone marrow STR-PCR testing are all 100% combined with the compatriot donor, but sTR-PCR appears 3 months after transplantation, sTR-PCR appears mixed, Chromosomal nucleotypes appear mixed chromosomes; up to 9 months after transplantation, the patient's bone marrow STR-PCR shows mixed chimeric, non-blood cord blood is dominant (Table 1), chromosome nucleotype changes to 46, XY? Patients review blood routine stability every month after transplantation (Table 2), bone marrow images are in disease relief? Patient immunofunction monitoring see 2?2 discuss theAA is a hematopoietic stem cell failure disease, SAA and VSAA due to persistent granulocytic deficiency? Platelet severity reduction, leading to severe infection? High risk of bleeding, high mortality rate? 2017 Chinese expertconsensus pointed out that for sAA patients aged 35 to 50 have a compatriot HLA all-in-one donor, can be To carry out MSD-HSCT? Compatriot all-in-one allogeneic stem cell transplant treatment SAA can get more than 80% of the total survival of 5 years (3-4)? The patient has two siblings, HLA matching and compatriot son 10/10 all-in-one, so we carried MSD-HSCT for the patient? The EBMT manual states that for recipients of MSD-HSCT, the recipient needs to infuse the donor stem cell CD34 plus the number of cells 2 x 106/kg (recipient weight) to meet the stem cell implant requirements, and for bone marrow failure diseases, such as S AA, in order for the recipient to obtain hematopoietic stem cell implantation, the number of CD34-cells requiring infusion donor hematopoietic stem cells is above 3 x 106/kg? But the patient's compatriot donor had serious adverse reactions during the peripheral blood stem cell collection process, and was forced to Early termination of collection? The total number of bone marrow and peripheral blood CD34 plus cells collected from fellow donor donors is only 1/3 of the number required by implantation? At this time, there are 3 paths before us: (1) risking re-collecting the donor's hematopoietic stem cells; (2) patients only intake the hematopoietic stem cells collected; (3) adding a third-party hematopoietic stem cell joint injection to carry out a double transplant? In the case of the donor can not tolerate stem cell collection, stem cell collection can not be forcibly carried out, and the patient is SAA, bone marrow hematopoietic stem cells and microenvironment is very poor, allogeneic hematopoietic stem cell infusion is too small, it is likely to lead to the patient's implant failure or poor implantation, the risk of death increased; Stem cells from 2 different types of donors? Zhang Xiaoming and others (2003) found in the mouse model of 3 allogeneic bone marrow transtransplants found that mice with multiple stem cells had the longest survival time compared with mice infusion of a stem cell, and a GVHD had the lowest incidence? Wang Xiaona and others (2017) re-in-transmission of H-2 monosple mice in CB6F1 mice in time to H-2 monotomaThe results showed that the aGVHD and lethality rates of dual donor cell infusion mice were significantly lower than those of the classical transplant groupThe above two models provided the theoretical basis for double transplantation? Xu Liyuan and others (2011) performed a single-polypial hematopoietic stem cell transplant on 5 SAA cases combined with umbilical cell interstitial stem cell infusion, all obtained hematopoietic reconstruction, and 4 patient-free survival? Xu et al(5) again expanded the sample size, in 24 patients with SAA patients monoploid hematopoietic stem cells combined with non-blood cord interstitial stem cell infusion therapy, and found that double transplantation can promote stem cell implantation and reduce the occurrence of severe aGVHD, safe and effective in AA treatment? Liu et al(6) performed a monoploid transplant on 44 Patients with AwyllM-Interstitial Stem Cell Transplant, and all but 3 patients died of complications early after transplantation, and all 41 patients received hematopoietic reconstruction, of which 29.3% had II-IV .DegreeaGVHD, occurrence cGVHD is 14.6%, 1 year total survival rate of 77.3%? Double transplantation is generally used in the replacement donor hematopoietic stem cell transplantation, cord blood transplantation? The reason for the HLA incomplete match is the decrease in implantation rate? The increased incidence of GVHD and other risks, affecting the efficacy of transplantation patients? In which the purpose of adding third-party cells is to promote the target donor stem cell implantation, reduce the occurrence of aGVHD? Although the patient is a fellow all-in-one donor, because the number of CD34 plus cells collected is likely to affect stem cell implantation, the probability of implant failure is greater, if the patient has failed implantation, only a second donor hematopoietic stem cell rescue can be transplanted again Therefore, according to the dual transplant theory, we directly infuse a non-blood cord blood stem cell for the patient, the patient successfully obtained hematopoietic reconstruction, the disease was alleviated? More interestingly, the patient began to appear in the 3 months after the transplant mixed chimeric, 6 months after the transplant patient hematopoietic cells completely transformed into the source of umbilical blood, the patient is currently nearly 10 months after transplantation did not occur acute chronic GVHD, good quality of life? MSD-HSCT joint non-blood cord blood double transplantation has not been documented, this case of patients in the case of fellow all-in-one donors can not provide enough hematopoietic stem cells to jointly carry out non-blood cord blood transplant success, save the patient's life, get clinically better efficacy?References?