Intrapartum Synthetic Oxytocin and Its Effects on Maternal Well-Being at 2 Months Postpartum.

BACKGROUND: Synthetic oxytocin (synOT) is commonly used in labor management to induce and augment labor, and to prevent postpartum hemorrhage. However, its long-term consequences for maternal health and behavior are largely understudied. We examined the relationship between synOT and maternal oxytocin levels, breastfeeding, and maternal mental health at 2 months postpartum. METHODS: Women were recruited during pregnancy or within 48 hours of giving birth through obstetric practices and hospitals. A total of 386 women were visited in their homes at 2 months postpartum, where they completed questionnaires assessing breastfeeding, depression, anxiety, posttraumatic stress, and somatization. Oxytocin levels were obtained from blood samples and synOT dosage information was gathered from hospital charts. RESULTS: Intrapartum synOT dose was positively correlated with endogenous oxytocin levels at 2 months postpartum. Women who were exclusively breastfeeding at 2 months postpartum had received significantly less synOT compared with their nonexclusively breastfeeding counterparts. Higher synOT dose was associated with greater depressive, anxious, and somatization symptoms. SynOT dose was not associated with perinatal posttraumatic stress. CONCLUSIONS: The widespread use of synOT in managed labor warrants caution, as the influence of synOT on a new mother's well-being is evident at 2 months postpartum.

Attachment security and recent stressful life events predict oxytocin levels: a pilot study of pregnant women with high levels of cumulative psychosocial adversity.

PURPOSE: Recent reports indicate that prenatal levels of the neuropeptide oxytocin (OT) are inversely related to depressive symptomatology and positively associated with more optimal interactive behaviors in mothers with high levels of cumulative psychosocial adversity (CPA). In the present pilot study, we aimed to identify factors associated with high versus low levels of OT in pregnant women with high levels of CPA. We hypothesized that insecurely attached women, and those who recently experienced stressful life events (SLE), would have lower levels of prenatal OT. METHODS: Thirty pregnant women with mood and anxiety disorders and high levels of CPA were recruited from the perinatal mental health service of a general hospital. Participants completed self-report measures of psychosocial stress and adult attachment style, and blood was then drawn to assess OT. RESULTS AND CONCLUSIONS: Lower OT levels were found among those who were insecurely attached, and among those who experienced SLE within the last year. In a multiple linear regression, both attachment security and SLE significantly contributed to a model of prenatal OT levels. These individual difference factors explained 38% of the variance in prenatal OT, which may in turn predict poorer maternal mental health and caregiving outcomes during the postpartum period.

MATERNAL MENTAL HEALTH MODERATES THE RELATIONSHIP BETWEEN OXYTOCIN AND INTERACTIVE BEHAVIOR.

Mothers with mood or anxiety disorders exhibit less optimal interactive behavior. The neuropeptide oxytocin (OT) has been linked to more optimal interactive behaviors in mothers without mental illness, and it may play a particularly beneficial role in mothers with mood or anxiety disorders given its antidepressant and anxiolytic functions. We compared the relationship between OT and interactive behavior in mothers with and without mental health problems. Participants included 20 women diagnosed with postpartum mood or anxiety disorders (clinical sample) and 90 women with low levels of depression and anxiety during pregnancy and postpartum (community sample). At 2 months' postpartum, blood was drawn to assess maternal OT levels, and mother-infant interaction was coded for maternal sensitivity, intrusiveness, remoteness, and depressiveness. Clinical mothers exhibited less sensitive, more intrusive, and more depressive interactive behaviors than did community mothers. The groups did not differ in OT levels. Mothers with higher OT levels were less intrusive with their infants. Higher OT levels were associated with less depressive interactive behavior only in clinical mothers. OT was associated with positive interactive behaviors in both groups. In clinical mothers, the calming and soothing effects of OT may promote more relaxed, energetic, and infant-focused interactive behaviors.

Single infusion of donor mononuclear early apoptotic cells as prophylaxis for graft-versus-host disease in myeloablative HLA-matched allogeneic bone marrow transplantation: a phase I/IIa clinical trial.

Because of its potent immunomodulatory effect, an infusion of donor mononuclear early apoptotic cells (ApoCell) was tested in addition to cyclosporine and methotrexate as prophylaxis for acute graft-versus-host disease (GVHD) after HLA-matched myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from a related donor. In a phase I/IIa clinical trial, we treated 13 patients (median age, 37 years; range, 20 to 59 years) with hematologic malignancies: 7 patients with acute lymphoblastic leukemia, 5 patients with acute myeloid leukemia, and 1 patient with chronic myeloid leukemia, who received conventional myeloablative conditioning, with 35, 70, 140, or 210 × 10(6) cell/kg of donor ApoCell, on day -1 of transplantation. Engraftment was successful in all patients with median time to neutrophil recovery of 13 days (range, 11 to 19), and platelet recovery of 15 days (range, 11 to 59). Serious adverse effects were reported on 10 occasions in the trial, all of which were considered unrelated (n = 7) or unlikely to be related (n = 3) to ApoCell infusion. The nonrelapse mortality at day 100 and 180 after transplantation was 7.7% and the overall survival at 100 and 180 days after transplantation was 92% and 85%, respectively. All ApoCell preparations showed an in vitro significant tolerogenic effect upon interaction with dendritic cells. The overall incidence of acute grades II to IV GVHD was 23%, whereas among those receiving the 2 higher doses (n = 6), the rate was 0%. These results suggest that a single infusion of donor ApoCell in HLA-matched allogeneic HSCT is a safe and potentially effective prophylaxis for acute GVHD occurring after myeloablative conditioning. No dose limiting toxicity was observed. (Clinicaltrials.gov no. NCT00524784).

A retrospective review of the outcome after second or subsequent allogeneic transplantation.

The failure of allogeneic stem cell transplant (allo-SCT) is cumbersome. We analyzed our experience in a second allo-SCT. Between the years 1981 and 2007, 144 patients underwent 2 or more allo-SCT. The first to second transplant interval ranged from 18 days to 13.25 years (median 98 days). The most frequent indications for the second SCT were activity of the basic disease (78), rejection (37), and engraftment failure (25). Twenty-nine of the 144 (20%) patients transplanted survived more then a year with treatment-related mortality of 45.5% as the leading cause of death. Interestingly, despite the low rate of graft-versus-host disease (GVHD) prophylaxis used, only 51 and 16 of the patients developed acute and chronic GVHD (aGVHD, cGVHD), respectively. Factors indicating higher likelihood for survival were nonmalignant disease, a nonrelapse indication for the second SCT, full HLA-matching, and the use of reduced-intensity conditioning (RIC). Age at transplantation, time interval between transplants, the development of GVHD, conditioning regimen, GVHD prophylaxis, or graft source were not shown to influence the prognosis. With a median follow-up of 4.5 years, 25 patients (17.2%) are alive, and 18 are disease-free. We conclude that although toxic, a second allo-SCT can lead to long-term survival.

A new induction protocol for the control of steroid refractory/dependent acute graft versus host disease with alefacept and tacrolimus.

BACKGROUND AIMS: We have shown previously that alefacept is effective in acute steroid resistant/dependent and chronic extensive graft versus host disease (GvHD) with a protocol using timings similar to those used for psoriasis treatment. In this study, we describe the use of an alefacept induction (e.g. for 7 consecutive days) followed by a bi-weekly maintenance treatment in combination with tacrolimus for acute steroid resistant/dependent GvHD 1, 3. METHODS: Sixteen patients were treated in this cohort, most with refractory GvHD. The pre-treatment GvHD grade ranged from 2 to 4 (median 3), involving the skin 16, gut 11 and liver 5. RESULTS: Twelve out of the 16 patients showed a response. As with the first protocol, the response of GvHD in the skin was fastest. In contrast to our previous protocol, however, the gastro-intestinal (GI) GvHD response was faster (P=0.05 compared with the first cohort). A hepatic response was seen in 4/6 patients and was complete in three. All responses were durable, including mucocutaneous, gut and liver GvHD. In all responding patients we were able to decrease the steroid dose significantly and in seven it was completely withdrawn. CONCLUSION: Alefacept induction is safe in acute steroid resistant/dependent GvHD and may be more effective therapeutically than our previous alefacept protocol. We speculate that alefacept initiates an allo-versus-allo cellular effect through its Fc receptor.

Maternal oxytocin predicts relationship survival during the perinatal transition period: Preliminary evidence.

It is well-known that the neuropeptide oxytocin plays a critical role regulating the formation of adult-adult pairbonds in non-human animals, and recent work suggests oxytocin may similarly play an important role in romantic bonding in humans. Specifically, endogenous oxytocin is predictive of a host of relationship-enhancing behaviors, relationship quality, and even relationship survival amongst newly dating couples. This work suggests that oxytocin can buffer romantic relationships, possibly during especially difficult transition periods. One challenge that many couples face is the birth of a child: a joyous event, but one that is recognized as a major life stressor nonetheless. We aimed to investigate whether maternal oxytocin buffers the parent-partner relationship during the perinatal transition period. To test this, we analyzed data from a longitudinal study of child-bearing women (N = 269) in which endogenous oxytocin was measured in blood plasma during the 1st and 3rd trimesters and at 7-9 weeks postpartum; relationship status was assessed at the outset and 2.5 years postpartum. As predicted, lower maternal oxytocin was associated with greater risk for relationship dissolution by the time the child was a toddler (p < .05). These findings directly replicate research showing that endogenous oxytocin predicts relationship survival in dating couples, but in a novel interpersonal context. That said, only a very small number (N = 7) of couples separated; this, of course, is unsurprising given that the perinatal transition period is not a time when couples typically choose to terminate their relationship. Nonetheless, these findings must be considered preliminary until replicated in future research.

ABO incompatibility is associated with increased non-relapse and GVHD related mortality in patients with malignancies treated with a reduced intensity regimen: a single center experience of 221 patients.

The effect of ABO-incompatibility on transplantation outcome remains a controversial issue, with many of the reported studies showing conflicting results. In this study, we evaluate: the association between ABO-incompatibility and myeloid engraftment; the incidence and severity of acute and chronic graft-versus-host disease (GVHD); non-relapse mortality (NRM); GVHD-associated mortality, relapse and overall survival (OS). Our study includes 221 patients with malignant diseases treated in the same institution with the same reduced intensity regimen. Other variables known to affect the transplantation outcome such as age, disease, disease risk, and donor characteristics were well-balanced between ABO-matched and ABO-mismatched transplants. Analysis of our data shows increased incidence of NRM during the first months after transplantation in the groups of patients with major and minor ABO-incompatibility. Although neither incidence nor severity of GVHD differed significantly among the different groups, we found increased mortality associated with GVHD in the major ABO-incompatible groups. Long-term OS and relapse rate were not different, although we observed a trend for decreased OS during the first year post transplantation in the group of patients with major ABO-incompatibility. Our study showed that ABO-incompatibility has an adverse impact on the transplantation outcome.

Induction of late graft-versus-host disease in a patient post-allogeneic stem cell transplantation by progesterone in conjunction with donor lymphocyte infusion.

Patients after stem cell transplantation (SCT), often develop graft-versus-host disease (GVHD) which, although potentially dangerous, is associated with the beneficial graft-versus-leukemia (GVL) effect. Where there is high risk of disease recurrence, donor lymphocyte infusions (DLI) are given to provide long-term disease control. We present a patient treated with DLI 4 years post-SCT, who developed acute GVHD after administration of progesterone to induce menstruation. This rare allergic reaction warrants further investigation.

Improved immune function with donor B-cell infusion after semi-allogeneic bone marrow transplantation in mice.

BACKGROUND: Regeneration of the immune system after bone marrow transplantation (BMT) is a slow process, often prolonged by the development and treatment of graft vs. host disease (GVHD). Donor lymphocyte infusion using allogeneic T-cells is widely applied for the induction of GVHD, which is associated with the desired graft vs. leukemia effect. Due to the slow immune recovery, our objective was to accelerate the immune recovery post-BMT by B-cell injections. METHODS: T-cell-depleted stem cells obtained from female C57BL/6 (B6) mice were transplanted into lethally irradiated (Balb/c x C57BL/6) F-1 female mice. Seven days post-transplantation, murine B-cells of male C57BL/6 origin were infused into the T-cell-depleted chimeras. Thirty and 60 days post-transplantation, PCR analysis of the Y-chromosome was carried out to detect male B-cells in the transplant recipients. In order to evaluate the specific antibody response, the donors were immunized by specific T-cell-dependent and -independent antigens. RESULTS: None of the T-cell-depleted transplanted mice developed GVHD during a follow-up period of 650 days, whereas all non-T-cell-depleted recipients died. At 60 days post-transplantation, significantly higher levels of immunoglobulins (IgA, IgG1, IgG3 isotypes) were seen in chimeras supplemented with male B-cells than in chimeras reconstituted with T-cell-depleted stem cells alone. CONCLUSIONS: Our data document the feasibility of administering B-cell therapy post-allogeneic BMT to improve recovery of the humeral arm of the immune system while avoiding GVHD. Furthermore, post-transplant B-cell administration may have an important impact as an alternative to IV immunoglobulin infusions.

A non-myeloablative conditioning regimen in allogeneic stem cell transplantation from related and unrelated donors in elderly patients.

We describe our experience with the use of a single non-myeloablative preparative regimen in stem-cell transplantation (NST) in 37 heavily pretreated patients > or =55 years. The conditioning regimen consisted of fludarabine, low-dose busulfan, and antithymocyte globulin. Acute graft-versus-host disease (GVHD) grade III-IV and chronic GVHD developed in 15.6% and 44.4% of cases, respectively. With a median follow-up period of 22 (range 3-113) months, the 1-year overall survival and disease-free-survival were 55% and 53%, respectively, while the overall non-relapse mortality was 35%. In conclusion, reduced intensity stem cell transplantation is feasible and effective in patients > or =55 years. Age per se, should no longer be considered as a contra-indication to stem cell transplantation.

Successful transplantation of haploidentically mismatched peripheral blood stem cells using CD133+-purified stem cells.

OBJECTIVE: For recipients of haploidentically mismatched stem cell allografts, T-cell depletion is mandatory to prevent lethal graft-vs-host disease (GVHD). Prevention of GVHD can be accomplished by negative selection of T cells or positive selection of stem cells. Recently, a new method for positive selection of stem cells was introduced using monoclonal antibodies against CD133 antigen. We report five cases of successful application of immunomagnetic separation of CD133+ stem cells for haploidentically mismatched allogeneic stem cell transplantation. METHODS: Five patients with high-risk hematological malignancies, ages 7 to 63 years old (median, 17 years), underwent peripheral blood stem cell transplantation from haploidentically mismatched related donors. Conditioning protocol was tailored according to patient clinical situation and included combination of treosulfan/fludarabine/thiotepa/melphalan/Mabcampath. Two patients did not get thiotepa. One of them received a protocol that included infusion of 4.4 x 10(7) blood mononuclear cells from the donor (day -9), followed by a combination of fludarabine/cyclophosphamide/busulfex/MabCampath. Separation of CD133+ stem cells was done using CliniMACS with Miltenyi's CD133 reagent. RESULTS: The procedure was well tolerated by all patients. Early 3-lineage engraftment was documented and none exhibited immune-mediated rejection. Time to recovery of absolute neutrophils count above 0.5 x 10(9)/L and 1.0 x 10(9)/L was 10 to 15 days (median, 14) and 11 to 29 days (median, 15), respectively. Time for platelet recovery to values greater than 20 x 10(9)/L and greater than 50 x 10(9)/L ranged from 12 to 25 days (median, 13.5), and from 14 to 34 days (median, 16), respectively. Transplant-related mortality did not occur in any of the patients. CONCLUSION: Our successful pilot trial suggests that positive selection of CD133+ stem cells may be a useful method for safe transplantation with haploidentically mismatched stem cell allografts while avoiding lethal acute and chronic GVHD. Future studies will be required to assess the clinical benefits of stem cell purification with CD133+ in comparison with CD34+ stem cells.

Intracoronary administration of autologous bone marrow mononuclear cells after induction of short ischemia is safe and may improve hibernation and ischemia in patients with ischemic cardiomyopathy.

BACKGROUND: Recent studies suggest that myocardial administration of stem cells improves perfusion and function of ischemic myocardium. The present study evaluated the safety and efficacy of simple intracoronary administration of mononuclear autologous bone marrow (BM) cells in patients with ischemic cardiomyopathy without revascularization option. METHODS AND RESULTS: We enrolled 6 consecutive patients with ischemic cardiomyopathy, who were in New York Heart Association classes III to IV despite optimal medical treatment without revascularization options and who, on dobutamine stress echocardiograph (DSE), were found to have left ventricular ejection fraction < 35% with significant hibernation and ischemia in at least 2 myocardial segments. BM cell suspension was collected, and on the next day, during coronary angiography, mild ischemia was induced by a short balloon inflation in each coronary conduit with a TIMI flow of > or = 2 followed by slow infusion of up to 50 mL of BM cells suspension to each conduit. At baseline and 4 months' follow-up, patients underwent clinical evaluation, Holter monitoring, and DSE. BM infusion was successful in all patients. One patient developed postprocedure hypotension and troponin increase. At 4 months' follow-up New York Heart Association class improved from 3.5 +/- 0.5 to 2.3 +/- 1.0, P = .04, and resting ejection fraction improved from 25% +/- 7% to 28% +/- 8%, P = .055. We observed improvement in resting wall motion score only in the segments with hibernation in baseline DSE (2.3 +/- 0.5 to 2.0 +/- 0.6, P = .03) and improvement in high-dose dobutamine wall motion score, only in segments showing significant ischemia at baseline DSE (2.5 +/- 0.5 to 2.0 +/- 0.6, P = .001). There were no clinical arrhythmias or increased arrhythmia burden by Holter monitoring. CONCLUSIONS: In patients with severe symptomatic ischemic cardiomyopathy, mild induction of ischemia followed by intracoronary infusion of unmanipulated autologous BM is feasible and safe and may improve hibernation and ischemia.

Successful engraftment following allogeneic stem cell transplantation in very high-risk patients with busulfan as a single agent.

BACKGROUND AND OBJECTIVES: Busulfan is the most commonly used myeloablative alkylating agent, but is considered a poor anti-lymphocyte agent. Since engraftment of allogeneic stem cells depends not only on adequate immunosuppression but also on successful hematopoietic competition, and considering the fact that residual lymphocytes of host origin may play a beneficial role in preventing graft-versus-host disease (GVHD), we used low doses of oral busulfan as a single agent for conditioning prior to stem cell transplantation (SCT) in recipients of transplants from a variety of donors. DESIGN AND METHODS: Fifteen heavily pretreated high-risk patients (age 25-66, median 42 years) with hematologic malignancies were conditioned with busulfan alone, 4mg/kg/day for 2, 3, or 4 consecutive days. No additional pre- or post-transplant immunosuppressive agents were used in order to exploit the capacity of donor lymphocytes to induce graft-versus-malignancy (GVM) effects. RESULTS: Conditioning was well tolerated, trilineage engraftment was documented in all patients and none exhibited immune-mediated rejection. Time to recovery of absolute neutrophil count >0.5x10(9)/L and 1.0x10(9)/L was 12 - 38 (median 15) days and 12 - 41 (median 15) days, respectively. The time to platelet recovery >or=20 and >or=50x10(9)/L ranged from 0 to 26 (median 11) days, and from 0 to 83 (median 14) days, respectively. Acute GVHD (

Early-onset Guillain-Barré syndrome associated with reactivation of Epstein-Barr virus infection after nonmyeloablative stem cell transplantation.

We report a case of early-onset acute Guillain-Barre syndrome associated with reactivation of Epstein-Barr virus (EBV) infection after nonmyeloablative stem cell transplantation (NST). Reactivation of EBV infection preceded disease onset, and the virus load increased concomitantly with disease progression (doubling time, 2.7 days). This case raises concern about the expanding scope of manifestations associated with reactivation of EBV infection after NST.

Autologous transplant in multiple myeloma with an augmented conditioning protocol.

We compared the tolerability and anti-myeloma effect of two conditioning regimens for autologous stem cell transplant (auto-SCT) in consecutive groups of patients. Protocol 1 was the earlier, and consisted of the combination of three agents in a sequential manner, including etoposide, thiotepa and melphalan (n = 29), while protocol 2 employed melphalan alone (n = 34). The two groups were comparable (other than younger age in protocol 1). Conditioning with protocol 1 seemed more toxic, as expressed by the higher number of febrile days and higher demand for parenteral nutrition. This was not expressed with longer admission time. With 108 and 60 months' median follow-up, respectively, the median survival in patients treated by protocol 2 (melphalan 200 mg/m(2)) was reached at 59 months, while the median survival was not yet reached in patients treated with protocol 1 (p = 0.039). The time to progression was significantly longer with protocol 1 (median 44 months vs. 17 months with protocol 2, p = 0.033). Confounded by the small number of patients, conditioning with melphalan augmented by etoposide and thiotepa in a sequential manner is slightly more toxic than melphalan alone and may benefit patients with myeloma undergoing auto-SCT.

Enhanced survival and neurite network formation of human umbilical cord blood neuronal progenitors in three-dimensional collagen constructs.

Umbilical cord blood (CB) stem cells have been proposed for cell-based therapeutic applications for diverse diseases of the CNS. We hypothesized that tissue-engineering strategies may extend the efficacy of these approaches by improving the long-term viability and function of stem cell-derived neuronal progenitors. To test our hypothesis, we explored the survival and differentiation of human CB-derived neuronal progenitors (HUCBNP) in a three-dimensional (3D) collagen construct. In contrast to two-dimensional culture conditions, the cells survived in 3D for an extended period of time of more than 2 months. Under 3D conditions, HUCBNP underwent spontaneous neuronal differentiation, which was further enhanced by treatment with neuronal conditioned medium (CM) and nerve growth factor (NGF). Neurite outgrowth, quantified by assessing the fractal dimension (D f) of the complex neuronal networks, was significantly enhanced under 3D conditions in the presence of CM/NGF, concomitant with a reduced expression of the early neuronal marker nestin (1.9-fold), and increased levels of mature neuronal markers such as MAP-2 (3.6-fold), ß-tubulin (1.5-fold), and neuronal specific enolase (6.6-fold) and the appearance of the synaptic marker synaptophysin. To assess the feasibility for clinical usage, HUCBNP were also isolated from frozen CB samples and cultured under 3D conditions. The data indicate the essential complete preservation of neurotrophic (survival) and neurotropic (neurite outgrowth) properties. In conclusion, 3D culture conditions are proposed as an essential step for both maintenance of CB neuronal progenitors in vitro and for investigating specific features of neuronal differentiation towards future use in regenerative therapy.

Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine-based preparative regimen.

We reviewed our experience in the treatment of 13 patients with severe acquired aplastic anaemia, using a newly developed non-myeloablative regimen consisting of fludarabine (total dose 180 mg/m2), cyclophosphamide (total dose 120 mg/kg), and antithymocyte globulin (total dose 40 mg/kg). All except one patient received multiple transfusions and had failed prior immunosuppressive treatment. Twelve out of 13 patients achieved sustained engraftment. One patient was not evaluable for engraftment because of early death on day +10. None of the patients developed graft failure. Mucositis of mild-to-moderate severity was the only observed regimen-related toxicity. The cumulative incidence of acute graft-versus-host disease (GvHD) grade II-IV and III-IV was 8.3% and 0%, respectively. With a median follow-up period of 45 months, the 5-year overall survival probability was 84%. Eight out of 11 surviving patients have been followed for more than 1 year and only one developed limited chronic GvHD. All patients enjoy a normal life style, with a Karnofsky score of 100%, and all except three, followed for 3, 5 and 6 months respectively, are free of any immunosuppressive medication. The results of this study look promising, while prospective clinical trials may be required to confirm the benefits of this regimen as an alternative to existing protocols.

Granulocyte colony stimulating factor does not induce long-term DNA instability in healthy peripheral blood stem cell donors.

To establish the safety of using G-CSF in healthy PBSC donors, we prospectively determined the degree of DNA destabilization in peripheral blood WBC. Donors were treated with SC G-CSF for 5 days. A baseline sample of peripheral blood was collected before G-CSF treatment and consecutive samples were collected on day 5, 1 month, and 2 months after treatment. The extent of double-stranded DNA relaxation and de novo synthesis of DNA was determined in each sample. We found that both parameters of DNA destabilization were significantly increased after 5 days of G-CSF and returned to baseline level at 1 and 2 months. We assume that these findings suggest that rhG-CSF administration to healthy PBSCT donors for 5 days may be a safe procedure.

Allogeneic stem cell transplantation for the treatment of diseases associated with a deficiency in bone marrow products.

Our understanding of the pathophysiology of hematopoietic failure associated syndromes led to the developmental of potentially curative procedures for the treatment of many diseases including Severe aplastic anemia, Fanconi's anemia, Primary immunodeficiency, Osteopetrosis, and Metabolic diseases. Although the number of patients that were transplanted for bone marrow deficiency diseases is relatively low as compared to patients with hematological malignancies, the impact on the knowledge of hematopoiesis and transplantation biology is tremendous. Moreover, the patient's average young age suffering from these diseases further encourage searching for curative approaches. Lucking a fully MHC matched donor, remained a significant obstacle in stem cell transplantation for non-malignant hematological disorders. Lessons from attempts to cure aplasic anemia with bone marrow transplantation guided us to the improvement of pretransplant conditioning regimens and prevention of graft versus host reactions after transplantation. Furthermore, in recent years optimization of disease specific protocol have been successfully designed and clinically applied.