Based on their findings, the researchers concluded that tobacco use may influence the biology of the disease and suggested that lower-risk myelodysplastic syndromes (MDS) patients may improve their outcomes if they discontinue any tobacco use.

The study results were presented during a poster session at the 2011 American Society of Hematology meeting last month.

Previous studies have linked tobacco use to the development of MDS. Other studies have shown that smoking decreases survival in certain MDS patients (see related Beacon news).

In the current study, researchers retrospectively compared the outcomes of MDS patients treated at the Moffitt Cancer Center who had a history of tobacco use (487 patients) to patients who had never used tobacco products (256 patients).

Tobacco use included cigarettes, cigars, pipes, snuff, and chew tobacco.

The researchers found that there were no statistically significant differences in age, type of MDS, presence of chromosomal abnormalities, red blood cell transfusion dependence, blood ferritin levels, or Vidaza (azacitidine) or Dacogen (decitabine) use between the tobacco users and the patients with no history of tobacco use.

However, the researchers found that among lower-risk MDS patients, the share of patients who had a history of tobacco use were significantly more likely to have chromosomal abnormalities that increased their risk of progressing to acute myeloid leukemia (9 percent of patients) than lower-risk MDS patients who had never used tobacco (2 percent).

Likewise, a higher percentage of lower-risk MDS patients who had a history of tobacco use progressed to acute myeloid leukemia (18 percent) than lower-risk MDS patients who did not have a history of tobacco use (10 percent). 

Tobacco usage did not affect the rate of disease progression for patients with higher-risk MDS.

After a median follow-up time of 55 months, the median overall survival for lower-risk MDS patients who had never used tobacco was significantly longer (69 months) than for lower-risk MDS patients who had used tobacco (48 months).

When the researchers compared data from lower-risk MDS patients who had formerly used tobacco to those of current tobacco users, they found that those who had given up tobacco had a median overall survival of 50 months, compared to 38 months for those still using tobacco.

Overall survival was similar among higher-risk MDS patients who had never used tobacco (22 months) and those who were tobacco users (18 months).

For more information, please see abstract 3790 at the ASH 2011 meeting website.

Specifically, the patients benefited from donor stem cell transplants without T-cells, a type of white blood cell.

Over 60 percent of patients experienced survival times greater than five years, and the rate of graft-versus-host disease, a common transplant-related complication, was low.

According to the researchers, these findings support the use of transplantation without T-cells in lower-risk myelodysplastic syndromes (MDS) patients.

The findings were presented at the 2011 American Society of Hematology (ASH) meeting last month.

Donor stem cell transplantation, also called allogeneic stem cell transplantation, is the only curative treatment for patients with MDS. However, this treatment is typically not considered early in the treatment plan for patients with lower-risk MDS due to the high risk of transplant-related complications.

Graft-versus-host disease is a common transplant-related complication, in which the donated stem cells attack the body’s cells. The rate of graft-versus-host disease decreases if mature T cells are removed from the donor cells before they are transplanted. T cells are a type of white blood cell that helps fight infections and tumor cells. They have also been identified as a cause of transplant rejection.

In the present study, researchers evaluated survival outcomes of 44 lower-risk MDS patients who underwent T cell-depleted stem cell transplantation early in their treatment plan. The median patient age was 37 years, and the median time from diagnosis to transplant was 0.6 years.

Prior to transplantation, patients received chemotherapy, with or without high-dose total body irradiation. Most of the patients also received anti-thymocyte globulin as preventative treatment for graft rejection. For 55 percent of patients, the transplant donor was a sibling, whereas 45 percent underwent transplantation with an unrelated donor.

The researchers found that the donated stem cells started producing white blood cells, a sign of a successful transplant, a median of 11 days after the transplant.

Five patients experienced graft failure, in which the body does not accept the donated cells. Four of these patients received second transplants, the common treatment for this complication.

The two-year and five-year survival rates were 70.1 percent and 63.3 percent, respectively.

Of the 44 patients included in the study, 14 percent developed graft-versus-host disease; half of the cases developed within the first 100 days after the transplant, the other half developed more than 100 days after the transplant.

As of May 2011, 36 percent of patients had died. Their causes of death included graft-versus-host disease (11 percent of patients), infections (11 percent), graft failure or poor graft function (7 percent), side effects of the preparative therapy prior to transplantation (5 percent), and lung cancer (2 percent).

For more information, please see abstract 3831 at the ASH 2011 meeting website.

These results were presented during a poster session at the 2011 American Society of Hematology (ASH) meeting last month.

Velcade (bortezomib) is currently approved by the U.S. Food and Drug Administration for the treatment of multiple myeloma and mantle cell lymphoma.

Belinostat (PXD 101), which is being developed jointly by the American company Spectrum Pharmaceuticals (NASDAQ: SPPI) and the Danish company TopoTarget, belongs to a class of drugs known as histone deacetylase (HDAC) inhibitors.  HDAC inhibitors work by increasing the production of proteins that slow cell division and cause cell death.

Zolinza (vorinostat), which is also being investigated as a potential treatment for myelodysplastic syndromes (MDS), belongs to the same class of drugs as belinostat and has shown promising results in combination with Vidaza (azacitine) in MDS patients with poor health (see related Beacon news).

Previous clinical trials have shown that treatment with Velcade or belinostat alone is not effective against MDS.

However, proteasome inhibitors such as Velcade and HDAC inhibitors such as belinostat have been shown to act synergistically, prompting the researchers to investigate whether a Velcade-belinostat combination may be effective for patients with blood cancers.

The primary goal of this Phase 1 trial was to determine the maximum safe dose of Velcade and belinostat for use in future Phase 2 trials.

So far, 13 patients with acute myeloid leukemia, chronic myelogenous leukemia, or MDS with a median age of 59 years have enrolled in the study.  The participants had received a median of two prior treatments.

During a 21-day treatment cycle, the patients received 1.0 mg/m² to 1.3 mg/m² of Velcade on days 1, 4, 8, and 11 followed by 500 mg/m² to 650 mg/m² of belinostat on days 1 through 5 and days 8 through 12.

Of the 12 patients who were evaluated for response to the combination treatment,  8 percent achieved a complete response and 33 percent maintained stable disease.

Side effects included low white blood cell counts, low platelet counts, and nerve damage in the limbs.  The researchers did not observe any dose-limiting side effects.

For more information, please see abstract 2598 at the ASH 2011 meeting website.

The findings were presented at the 2011 American Society of Hematology (ASH) meeting in San Diego last month.

In France, chemotherapy is typically administered in a hospital. However, the French National Health Service allows home administration of some chemo­therapy treatments after the first treatment cycle.

A group of French researchers, therefore, sought to investigate if Vidaza (azacitidine) could be safely administered at home.

Sixty-eight patients, including 51 with myelodysplastic syndromes (MDS), volunteered for this study after receiving their first cycle of chemotherapy in the hospital. Forty-eight of the study patients were treated with Vidaza.

The study participants were divided into two groups. One group continued to receive all doses of Vidaza administered at a hospital.  The other group received Vidaza at a hospital the first day of every treatment cycle, but all other doses of Vidaza in the treatment cycle were administered at home.

The researchers compared the number of treatment cycles the patients were able to complete, the dosage patients were able to tolerate, and problems with administration for both patient groups.

Results showed that over the 18-month study period, both groups received a similar median number of treatment cycles.

The two groups also experienced similar side effects, delays between treatment cycles, and hospitalizations between cycles.

The researchers also observed a high level of patient satisfaction in the home administration group.

They reported that all patients in the home administration group agreed to continue at-home treatment.

In some cases, home administration of Vidaza was not possible because of infection, low blood cell counts, or drug availability.

According to the researchers, further randomized studies are planned to compare the quality of life between patients receiving chemotherapy in the hospital or at home.

For more information, please see abstract 1719 at the ASH 2011 meeting website.

The most common side effects were low blood cell counts, which required close monitoring. However, the study authors concluded from these results that the side effects were acceptable when compared to conventional chemotherapy, which is often ineffective and intolerable in high-risk patients.

Previous research has shown that the combination therapy of Vidaza (azacitidine) and Revlimid (lenalidomide) is effective and safe in patients with higher-risk myelodysplastic syndromes (MDS) (see related Beacon news).

Vidaza destroys rapidly dividing cells by removing methyl groups from DNA. Revlimid promotes cell death by preventing the growth of new blood vessels needed for tumor survival.

Researchers have recently proposed that the complementary mechanisms of Vidaza and Revlimid may produce additional benefits not seen in single-agent therapy.

In the present study, French researchers report their experience with Vidaza and Revlimid as a first-line therapy in eight patients with high-risk MDS or acute myeloid leukemia (AML) with chromosomal abnormalities. All of the patients had three or more abnormalities in their chromosomes, which is called a complex karyotype. The median patient age was 66.5 years.

The median time from diagnosis to the start of treatment was 3.5 months.

Five patients received 75 mg/m² of Vidaza on days 1 through 5, and three patients received 75 mg/m² on days 1 through 7 of a 28-day cycle. In addition, the patients received 10 mg of Revlimid on days 1 through 21. One patient received 5 mg of Revlimid.

Six of the eight patients responded to treatment: three with a complete response and three with a partial response. The two remaining patients experienced disease progression during treatment.

The initial response occurred at a median of 10 weeks after the treatment started. Four of the six responders relapsed at a median of 12 weeks after their initial response. The other two responding patients are still alive and in complete remission. Both patients received a donor stem cell transplant.

The median overall-survival and progression-free survival were 15 months and 9.5 months, respectively.

The major observed side effects were low blood cell counts. Seven of the eight patients experienced severe to life-threatening low platelet counts. Five patients developed severe to life-threatening low white blood cell counts, which often resulted in blood poisoning and, in two cases, hospitalization in the intensive care unit.

Five of the eight patients died. Two patients died because their disease was resistant to treatment. After initially responding to treatment, three patients died from disease progression.

For more information, please refer to the article in Leukemia (abstract).

The study authors found that treatment response rates in their trial were directly associated with the number of screening criteria patients met. For patients who met all screening criteria, 100 percent responded to therapy.

In myelodysplastic syndromes (MDS), the bone marrow produces an excess of developing blood cells that are unable to properly mature and function. These developing cells, called blasts, accumulate in the bone marrow, thereby inhibiting production of healthy blood cells.

In some types of MDS, the immune system attacks the bone marrow and prevents it from making healthy blood cells. As a result, scientists have recently proposed immunosuppressive therapy as a possible treatment for MDS. This therapy employs drugs that reduce the immune system’s response, thereby allowing the bone marrow to produce more blood cells.

Previous research into immunosuppressive therapy for MDS patients has shown that not all patients benefit from such treatment.  For some patients, the therapy can have a significant positive effect.  For other patients, the treatment can actually be detrimental.

Thus, scientists are working hard to find criteria that identify MDS patients most likely to respond to immunosuppressive therapy.

The National Comprehensive Cancer Network, an alliance of major U.S. cancer centers, has developed one set of such criteria.  They include: an International Prognostic Scoring System (IPSS) score no greater than 1, age no greater than 60 years, low blood cell counts, paroxysmal nocturnal hemoglobinuria (a condition characterized by red blood cell breakdown), and the presence of the HLA-DR15 gene.

However, according to the authors of the Chinese study, the response rates to immunosuppressive therapy based on these criteria have been mixed so far.

The study authors therefore decided to test an alternative set of screening criteria.

In their study, the Chinese researchers sought to determine the response rates and the rates of disease progression in low-risk MDS patients (IPSS score no greater than one) who received treatment with immunosuppressive therapy and who met at least one of the following criteria: presence of the HLA-DR15 gene, bone marrow cell counts of less than 30 percent, or abnormal T-cell function in the bone marrow.

The requirement related to T-cell function was included due to evidence that immunosuppressive therapy works, in part, by affecting the behavior of T cells.  T cells are white blood cells that play a critical role in the immune system’s response.

Patients were ineligible to participate in the Chinese study if they had at least 5 percent blasts in the bone marrow, a poor chromosomal profile (based on IPSS criteria), or non-blood related tumors.

A total of 71 patients met the eligibility criteria and were able to be evaluated for the study, which recruited patients from August 2006 to December 2010.  The median age of patients in the study was 41, which is noticeably younger than the age of MDS patients in other trials investigating immunosuppressive therapy for MDS.

Most patients in the study received treatment with cyclosporine (Sandimmune); six patients received treatment first with anti-thymocyte globulin (ATG), followed by cyclosporine. These drugs target and reduce the number of circulating T cells.  They also are the drugs most commonly used in immunosuppressive therapy for MDS.

The study authors found that 77 percent of patients in the study experienced an improvement in red blood cell counts.  This compares to an average of 39 percent of patients achieving an improvement in red blood cell counts in four previous trials of immunosuppressive therapy for MDS reviewed by the Chinese researchers.

Of the patients who were dependent on red blood cell transfusions prior to immunosuppressive therapy in the Chinese study, about 64 percent achieved transfusion independence after therapy.

The authors of the current study determined that the blood cell response was associated with the number of eligibility criteria met. For patients who met one of the three key criteria, 63 percent responded to therapy. This percent increased to 83 percent for those who met two criteria and to 100 percent for those who met all three criteria.

After a median follow-up period of 24 months, 85 percent of patients were still alive. The major causes of death were severe infections or bleeding caused by bone marrow failure.  The median age of the patients who died during the study was 57.

After therapy, only one patient had his blast percentage increase to over 5 percent. Additionally, one patient transformed to leukemia, which, according to the study authors, is significantly lower than the rate found in previous studies (1.4 percent versus 11.8 percent).

The study authors acknowledge, however, that the strict eligibility criteria for their study probably contributed to the low leukemic transformation rate and the high share of patients who experienced an improvement in red blood cell counts .

For more information, please refer to the article in the American Journal of Hematology (abstract).

“In both [standard- and high-risk] MDS, elevated ferritin has a negative effect on the outcomes of transplantation,” said study author Dr. Takayoshi Tachibana of the Yokohama City University Medical Center in Yokohama, Japan.

Dr. Tachibana pointed out that patients with elevated ferritin levels should nevertheless undergo stem cell transplantation because “We think transplantation is the most promising therapy [for MDS patients].”

Instead he suggested that “The mechanism or nature of ferritin must be explored and a novel [approach] for reducing pre-transplant ferritin must be devised.”

Patients with MDS frequently have low red blood cell counts, a condition known as anemia. Red blood cell trans­fusions can be used to increase the cell counts. However, receiving repeated red blood cell trans­fusions can lead to excess iron in the blood, also known as iron overload.

Ferritin is an iron storage protein that can be used as an indicator for the amount of iron in a patient’s blood. “In most MDS patients, elevated ferritin [in the blood] is related to red blood cell trans­fusion,” explained Dr. Tachibana.

According to the Japanese researchers, elevated ferritin levels prior to stem cell transplantation have been shown to have a negative impact on outcomes in patients with higher-risk MDS.

“Elevated ferritin [in the blood] seems to be associated with a higher risk of complication after transplantation,” said Dr. Tachibana.

However, little is known about the effects of ferritin levels in lower-risk patients who undergo a stem cell transplant.

In this study, the researchers retrospectively analyzed data from 261 patients with different blood cancers of varying severity to determine the impact of pre-transplant ferritin levels on outcomes.

Of the 261 patients included in the analysis, 36 (14 percent) had MDS. The rest of the patients had either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL).  (Unless otherwise specified, all results discussed in the rest of this article will be for patients with any of the three blood cancers covered by the study — not just for patients with MDS.)

The median age of the patients in the study was 43. All patients were treated at three hospitals in Japan between January 2000 and December 2008.

For their analyses, the authors of the study divided patients into two groups based on their disease severity: standard-risk and high-risk.

One quarter of the 36 MDS patients included in the analysis were categorized as having standard-risk disease, and three quarters were categorized as having high-risk disease.

Ferritin levels were measured one month before the patients began preparative chemotherapy for their stem cell transplants.

Patients were placed in the low ferritin group if they had less than 1,000 ng/mL ferritin in their blood or in the high ferritin group if they had 1,000 ng/mL or more ferritin in their blood.

The median ferritin level was 970 ng/mL. The researchers found that high-risk patients were significantly more likely to have high ferritin levels.

After five years, more patients with standard-risk disease were alive (60 percent) than patients with high-risk disease (25 percent).

Similarly, more patients in the low ferritin group were alive (54 percent) than patients in the high ferritin group (36 percent) after five years.

When the researchers divided the patients by disease-risk groups, they found that low ferritin levels had a positive impact on outcomes in both standard-risk and high-risk patients.

Standard-risk patients with low ferritin levels had significantly better overall survival after five years (64 percent) compared to standard-risk patients with high ferritin levels (54 percent).

In the high-risk group, patients with low ferritin levels also had significantly better overall survival compared to patients with high ferritin levels (35 percent versus 16 percent).

High-risk patients with low ferritin levels were also significantly less likely to experience disease relapse (50 percent) than high-risk patients with high ferritin levels (72 percent).

The impact of ferritin levels on survival remained statistically significant when the researchers controlled for a number of patient characteristics that also could affect survival.

In addition, the effect of ferritin levels stayed significant even when the analysis focused only on the 36 patients in the study who had MDS.

As the researchers explain in their article, “When subgroup analysis was done for the underlying diseases, pre-transplant [ferritin level] was a significant predictor of the outcome for patients with AML or MDS …”

Acute graft-versus-host disease, a transplant-related complication that develops within 100 days after transplantation, occurred in 107 of the 261 patients patients.   The development of acute graft-versus-host disease was not found to be related to a patient’s ferritin levels.

Patients who developed chronic graft-versus-host disease, which occurs more than 100 days post-transplant, had better overall five-year survival (67 percent versus 51 percent) than patients who did not have chronic graft-versus-host disease.

A total of 141 patients died during the study’s five years follow-up time; 43 percent died of disease relapse or disease progression and 57 percent died of other causes, including infection, organ failure, graft-versus-host disease, pneumonia, and transplant rejection or failure.

For more information, please see the study in the journal Leukemia & Lymphoma (abstract).

In particular, the researchers found that myelo­dys­plastic syndromes (MDS) patients with IDH1 mutations had a median overall survival of only 3 months compared to 29 months for MDS patients without the mutation.

This result, the authors write, “suggests a powerful adverse prognostic effect for mutant IDH1 in MDS.”

Isocitrate dehydrogenase (IDH) is an enzyme that plays an important role in the citric acid cycle, which itself is a key part of the way the body generates energy from food.

There are two subclasses of IDH, IDH1 and IDH2.

Mutations in the IDH enzymes prevent them from functioning properly. The mutations have been linked to brain tumors and to acute myeloid leukemia (AML).

According to the study authors, 10 percent of AML patients and 5 percent of myelodysplastic syndromes patients have IDH mutations.

Although previous studies have examined the impact of IDH mutations on the prognosis of patients with AML, this association has not yet been investigated for MDS.

In the present study, researchers studied the impact of IDH mutations in 227 MDS patients who had been seen at the Mayo Clinic between 2002 and 2005. The median patient age was 71 years.

The study authors found that 12 percent of patients had a mutation in the IDH gene (3 percent in IDH1, and 9 percent in IDH2).

At the time of the study’s publication, 81 percent of patients had died, and 18 percent had progressed to AML.

Half of the patients with IDH1 mutations had progressed to AML, compared to 19 percent of those with IDH2 mutations. All of the patients with IDH mutations who had progressed to AML died.

The study authors found that the presence of IDH1 mutations, but not IDH2 mutations, was associated with shortened progression-free and overall survival. They pointed out that this finding is similar to that observed in AML patients.

The median overall survival for patients with IDH1 mutations was three months compared to 29 months for patients without IDH1 mutations.  This substantial difference in survival between the two groups is very strong evidence of a link between the IDH1 mutation and shorter survival.

The median overall survival for patients with IDH2 mutations was 22 months, compared to 27 months for patients without IDH2 mutations.  The study authors determined, however, that this difference could be explained by chance variations in survival among MDS patients.  So the researchers could not safely conclude that IDH2 mutations are associated with shorter survival.

For more information, please refer to the study in Leukemia (abstract).

However, the study authors pointed out that this finding was only significant for patients with standard-risk disease. In patients with high-risk disease, the differences in survival were not statistically significant.

In addition, patients with standard-risk disease who received transplants from related donors with a mismatch at the HLA B gene experienced lower overall survival rates than patients who had related donors with mismatches at other HLA genes.

The study authors acknowledged that genetic similarities within the Japanese population might have contributed to a lower rate of treatment-related complications for patients who used matched unrelated donors. Previous studies conducted in other countries had found no difference in overall survival between the patients who received stem cell transplants from matched unrelated donors and those who received transplants from related donors with one mismatch.

Physicians have found that the selection of a stem cell donor plays a significant role in the success of stem cell transplants. In selecting a donor, physicians compare the genetic sequence of the human leukocyte antigen (HLA) from the recipient and from the donor. HLA is a cell surface protein that assists the immune system in differentiating between the body’s own tissues and foreign materials.

It is preferred for the donor to be a sibling with an identical HLA genetic sequence; however, not all recipients have a matched sibling donor. In these cases, an HLA-matched unrelated donor is often used for the transplant.

For patients with rare HLA genetic sequences, it still may be difficult to find an HLA-matched donor, related or unrelated. Previous studies have shown that patients who receive transplants from HLA-mismatched donors experienced higher rates of transplant failure and lower overall survival rates.

In the present study, the Japanese researchers compared clinical outcomes from transplants with a related donor with one HLA mismatch and from transplants with an HLA-matched unrelated donor.

They retrospectively analyzed data collected from patients with various blood cancers who had received transplants in Japan between 2001 and 2008.

Of the 779 patients included in the analysis, 327 received transplants from HLA-mismatched related donors, and 452 received transplants from HLA-matched unrelated donors.

The patients who used HLA-mismatched related donors were generally younger (median age of 45 years versus 48 years) and more likely to have high-risk disease (41 percent versus 29 percent) than those who used HLA-matched unrelated donors. Sixteen percent of the patients were diagnosed with myelodysplastic syndromes (MDS).

The two-year overall survival rate for patients who used HLA-matched unrelated donors was 59 percent, compared to 44 percent for patients who used HLA-mismatched related donors.

The study authors determined that the use of an HLA-mismatched related donor significantly shortened overall survival. Other factors that negatively impacted overall survival included patient age of at least 50 years and high-risk disease.

The impact of the HLA mismatch on outcome depended on whether the patients had standard-risk or high-risk disease. In patients with standard-risk disease, the overall survival was significantly higher for patients who received transplants from HLA-matched unrelated donors.

However, in patients with high-risk disease, there was no significant difference in overall survival between patients who received stem cell transplants from matched unrelated donors and those who received transplants from related donors with one mismatch.

The study authors also examined whether the specific gene at which the HLA mismatch occurs impacted overall survival. They found that patients who received transplants from related donors with a mismatch at the HLA B gene experienced the shortest overall survival and the highest rates of transplant-related death. However, the HLA B mismatch only affected overall survival significantly for patients with standard-risk disease.

For more information, please refer to the article in the journal Blood (abstract).

Cytokines are hormone-like molecules used by the body to transmit signals between cells.  Most of the time, cytokines transmit signals related to immune system issues — for example, whether more white blood cells are needed in a specific part of the body to fight an infection.

During the course of their study, the Mayo researchers found that myelodysplastic syndromes patients with abnormally high levels of at least one of the cytokines CXCL10, IL-6, or IL-7 had significantly shorter survival times than patients with normal levels of all three cytokines.

More specifically, MDS patients in the Mayo study who had normal levels of the three cytokines lived three times as long as patients who had very high levels of either CXCL10, IL-6, or IL-7.

In the near term, the Mayo findings may help physicians select better treatment options for their MDS patients.  If, for example, an MDS patient has abnormally high levels of  CXCL10, IL-6, or IL-7, a physician might opt to treat the patient’s MDS particularly aggressively.

In the longer term, the researchers’ findings may help scientists find new treatments for MDS.

The Mayo research was sparked by recent studies suggesting there may be a link between cytokine levels and disease outcomes in at least two types of blood cell cancer, myelofibrosis and large-cell lymphoma.

In the present study, the Mayo Clinic researchers investigated whether blood cytokine levels may also be linked to disease prognosis in MDS. In addition, they wanted to find out if cytokine levels were associated with certain patient characteristics.

The researchers analyzed the levels of 31 different cytokines in 78 patients with MDS as their primary cancer, and then compared the cytokine levels in the MDS patients to the levels in 35 healthy individuals from a control group.

The median age of the MDS patients was 72 years, and 75 percent had lower-risk MDS. The majority of patients were not receiving MDS-targeted therapy when blood plasma samples were collected.

The researchers found that the levels of 18 cytokines were significantly higher in MDS patients than in the healthy individuals. Only one cytokine, RANTES, was significantly lower compared to the control group.

They also found that elevated levels of the cytokine IL-8 were associated with higher-risk disease according to the International Prognostic Scoring System (IPSS), dependence on red blood cell transfusions, a higher count of immature stem cells (blasts) in the bone marrow, and female gender.

Increased levels of CXCL10 were associated with blasts circulating outside of the bone marrow and low platelet counts.

Increased levels of RANTES were also associated with low platelet counts, whereas decreased levels of IL-17 were associated with red blood cell transfusion dependency.

All other cytokines were not significantly associated with any patient characteristics.

The median follow-up for all MDS patients in the study was 24 months. MDS patients who lived for the entire course of the study were followed for a median of 31 months.  By the end of the study, 59 percent of the MDS patients died.

The researchers key finding was that that very high levels of CXCL10, IL-6, and IL-7 were associated with shorter survival. MDS patients with normal levels of these three key cytokines lived three times longer than patients with abnormally high levels of one or more of the cytokines (76 months versus 25 months).

The impact of high levels of CXCL10, IL-6, and IL-7 was still measurable — and statistically significant — even when the researchers controlled for patients’ IPSS (risk) category, blood transfusion dependence, and platelet levels.

About one quarter of the MDS patients in the study had normal levels of the three key cytokines.  The other MDS patients had abnormally high levels of at least one of the three key cytokines.

The researchers pointed out that CXCL10 had previously been identified as an independent factor of disease prognosis for myelofibrosis and large-cell lymphoma. According to the researchers, this finding suggests that CXCL10 is released in response to a general disease state, rather than as a response to a specific tumor.

More generally, however, it is not yet clear why elevated levels of the three key cytokines are associated with a poor MDS prognosis.

It could be that the high cytokine levels damage the body in various ways, thereby reducing survival.  High cytokine levels have been shown in other studies to have negative effects on the body.

Another possibility is that the high cytokine levels are simply a reflection of the fact that the MDS in these cases is particularly aggressive.

For more information, please refer to the study in the journal Leukemia (abstract).